Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells

Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Mohamed Abdouh [verfasserIn] Dana Hamam [verfasserIn] Zu-Hua Gao [verfasserIn] Vincenzo Arena [verfasserIn] Manuel Arena [verfasserIn] Goffredo Orazio Arena [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis

Übergeordnetes Werk:	In: Journal of Experimental & Clinical Cancer Research - BMC, 2008, 36(2017), 1, Seite 15
Übergeordnetes Werk:	volume:36 ; year:2017 ; number:1 ; pages:15

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13046-017-0587-0

Katalog-ID:	DOAJ001844105

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520			\|a Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
650		4	\|a Cancer patients’ serum
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650		4	\|a Tumor suppressor genes
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653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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allfields	10.1186/s13046-017-0587-0 doi (DE-627)DOAJ001844105 (DE-599)DOAJc717b1a1f3be4c5ba6755a588d7108af DE-627 ger DE-627 rakwb eng RC254-282 Mohamed Abdouh verfasserin aut Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dana Hamam verfasserin aut Zu-Hua Gao verfasserin aut Vincenzo Arena verfasserin aut Manuel Arena verfasserin aut Goffredo Orazio Arena verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 36(2017), 1, Seite 15 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:36 year:2017 number:1 pages:15 https://doi.org/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af kostenfrei http://link.springer.com/article/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 36 2017 1 15
spelling	10.1186/s13046-017-0587-0 doi (DE-627)DOAJ001844105 (DE-599)DOAJc717b1a1f3be4c5ba6755a588d7108af DE-627 ger DE-627 rakwb eng RC254-282 Mohamed Abdouh verfasserin aut Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dana Hamam verfasserin aut Zu-Hua Gao verfasserin aut Vincenzo Arena verfasserin aut Manuel Arena verfasserin aut Goffredo Orazio Arena verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 36(2017), 1, Seite 15 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:36 year:2017 number:1 pages:15 https://doi.org/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af kostenfrei http://link.springer.com/article/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 36 2017 1 15
allfields_unstemmed	10.1186/s13046-017-0587-0 doi (DE-627)DOAJ001844105 (DE-599)DOAJc717b1a1f3be4c5ba6755a588d7108af DE-627 ger DE-627 rakwb eng RC254-282 Mohamed Abdouh verfasserin aut Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dana Hamam verfasserin aut Zu-Hua Gao verfasserin aut Vincenzo Arena verfasserin aut Manuel Arena verfasserin aut Goffredo Orazio Arena verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 36(2017), 1, Seite 15 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:36 year:2017 number:1 pages:15 https://doi.org/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af kostenfrei http://link.springer.com/article/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 36 2017 1 15
allfieldsGer	10.1186/s13046-017-0587-0 doi (DE-627)DOAJ001844105 (DE-599)DOAJc717b1a1f3be4c5ba6755a588d7108af DE-627 ger DE-627 rakwb eng RC254-282 Mohamed Abdouh verfasserin aut Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dana Hamam verfasserin aut Zu-Hua Gao verfasserin aut Vincenzo Arena verfasserin aut Manuel Arena verfasserin aut Goffredo Orazio Arena verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 36(2017), 1, Seite 15 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:36 year:2017 number:1 pages:15 https://doi.org/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af kostenfrei http://link.springer.com/article/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 36 2017 1 15
allfieldsSound	10.1186/s13046-017-0587-0 doi (DE-627)DOAJ001844105 (DE-599)DOAJc717b1a1f3be4c5ba6755a588d7108af DE-627 ger DE-627 rakwb eng RC254-282 Mohamed Abdouh verfasserin aut Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes. Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dana Hamam verfasserin aut Zu-Hua Gao verfasserin aut Vincenzo Arena verfasserin aut Manuel Arena verfasserin aut Goffredo Orazio Arena verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 36(2017), 1, Seite 15 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:36 year:2017 number:1 pages:15 https://doi.org/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af kostenfrei http://link.springer.com/article/10.1186/s13046-017-0587-0 kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 36 2017 1 15
language	English
source	In Journal of Experimental & Clinical Cancer Research 36(2017), 1, Seite 15 volume:36 year:2017 number:1 pages:15
sourceStr	In Journal of Experimental & Clinical Cancer Research 36(2017), 1, Seite 15 volume:36 year:2017 number:1 pages:15
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Journal of Experimental & Clinical Cancer Research
authorswithroles_txt_mv	Mohamed Abdouh @@aut@@ Dana Hamam @@aut@@ Zu-Hua Gao @@aut@@ Vincenzo Arena @@aut@@ Manuel Arena @@aut@@ Goffredo Orazio Arena @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	568921380
id	DOAJ001844105
language_de	englisch
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Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. 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callnumber-first	R - Medicine
author	Mohamed Abdouh
spellingShingle	Mohamed Abdouh misc RC254-282 misc Cancer patients’ serum misc Exosomes misc Malignant transformation misc Horizontal transfer misc Tumor suppressor genes misc Genometastasis misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
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topic_title	RC254-282 Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells Cancer patients’ serum Exosomes Malignant transformation Horizontal transfer Tumor suppressor genes Genometastasis
topic	misc RC254-282 misc Cancer patients’ serum misc Exosomes misc Malignant transformation misc Horizontal transfer misc Tumor suppressor genes misc Genometastasis misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc Cancer patients’ serum misc Exosomes misc Malignant transformation misc Horizontal transfer misc Tumor suppressor genes misc Genometastasis misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc Cancer patients’ serum misc Exosomes misc Malignant transformation misc Horizontal transfer misc Tumor suppressor genes misc Genometastasis misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
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title_full	Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
author_sort	Mohamed Abdouh
journal	Journal of Experimental & Clinical Cancer Research
journalStr	Journal of Experimental & Clinical Cancer Research
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author_browse	Mohamed Abdouh Dana Hamam Zu-Hua Gao Vincenzo Arena Manuel Arena Goffredo Orazio Arena
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author-letter	Mohamed Abdouh
doi_str_mv	10.1186/s13046-017-0587-0
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title_sort	exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
callnumber	RC254-282
title_auth	Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
abstract	Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
abstractGer	Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
abstract_unstemmed	Abstract Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients’ sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients’ sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. Methods We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients’ sera or cancer patients’ sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts’ membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Results Cells treated with exosomes isolated from cancer patients’ sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits. Conclusion These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
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title_short	Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
url	https://doi.org/10.1186/s13046-017-0587-0 https://doaj.org/article/c717b1a1f3be4c5ba6755a588d7108af http://link.springer.com/article/10.1186/s13046-017-0587-0 https://doaj.org/toc/1756-9966
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author2	Dana Hamam Zu-Hua Gao Vincenzo Arena Manuel Arena Goffredo Orazio Arena
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