A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis
Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal...
Ausführliche Beschreibung
Autor*in: |
Giuseppina Augimeri [verfasserIn] Maria E. Gonzalez [verfasserIn] Alessandro Paolì [verfasserIn] Ahmad Eido [verfasserIn] Yehyun Choi [verfasserIn] Boris Burman [verfasserIn] Sabra Djomehri [verfasserIn] Santhosh Kumar Karthikeyan [verfasserIn] Sooryanarayana Varambally [verfasserIn] Johanna M. Buschhaus [verfasserIn] Yu-Chih Chen [verfasserIn] Loredana Mauro [verfasserIn] Daniela Bonofiglio [verfasserIn] Alexey I. Nesvizhskii [verfasserIn] Gary D. Luker [verfasserIn] Sebastiano Andò [verfasserIn] Euisik Yoon [verfasserIn] Celina G. Kleer [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2023 |
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In: JCI Insight - American Society for Clinical investigation, 2020, 8(2023), 18 |
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Übergeordnetes Werk: |
volume:8 ; year:2023 ; number:18 |
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Katalog-ID: |
DOAJ091026512 |
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(DE-627)DOAJ091026512 (DE-599)DOAJ0fdb611aabcf4f8398eea1d60e3165be DE-627 ger DE-627 rakwb eng Giuseppina Augimeri verfasserin aut A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance. Cell biology Oncology Medicine R Maria E. Gonzalez verfasserin aut Alessandro Paolì verfasserin aut Ahmad Eido verfasserin aut Yehyun Choi verfasserin aut Boris Burman verfasserin aut Sabra Djomehri verfasserin aut Santhosh Kumar Karthikeyan verfasserin aut Sooryanarayana Varambally verfasserin aut Johanna M. Buschhaus verfasserin aut Yu-Chih Chen verfasserin aut Loredana Mauro verfasserin aut Daniela Bonofiglio verfasserin aut Alexey I. Nesvizhskii verfasserin aut Gary D. Luker verfasserin aut Sebastiano Andò verfasserin aut Euisik Yoon verfasserin aut Celina G. Kleer verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 8(2023), 18 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:8 year:2023 number:18 https://doaj.org/article/0fdb611aabcf4f8398eea1d60e3165be kostenfrei https://doi.org/10.1172/jci.insight.164216 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2014 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 8 2023 18 |
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(DE-627)DOAJ091026512 (DE-599)DOAJ0fdb611aabcf4f8398eea1d60e3165be DE-627 ger DE-627 rakwb eng Giuseppina Augimeri verfasserin aut A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance. Cell biology Oncology Medicine R Maria E. Gonzalez verfasserin aut Alessandro Paolì verfasserin aut Ahmad Eido verfasserin aut Yehyun Choi verfasserin aut Boris Burman verfasserin aut Sabra Djomehri verfasserin aut Santhosh Kumar Karthikeyan verfasserin aut Sooryanarayana Varambally verfasserin aut Johanna M. Buschhaus verfasserin aut Yu-Chih Chen verfasserin aut Loredana Mauro verfasserin aut Daniela Bonofiglio verfasserin aut Alexey I. Nesvizhskii verfasserin aut Gary D. Luker verfasserin aut Sebastiano Andò verfasserin aut Euisik Yoon verfasserin aut Celina G. Kleer verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 8(2023), 18 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:8 year:2023 number:18 https://doaj.org/article/0fdb611aabcf4f8398eea1d60e3165be kostenfrei https://doi.org/10.1172/jci.insight.164216 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2014 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 8 2023 18 |
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Giuseppina Augimeri |
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Giuseppina Augimeri Maria E. Gonzalez Alessandro Paolì Ahmad Eido Yehyun Choi Boris Burman Sabra Djomehri Santhosh Kumar Karthikeyan Sooryanarayana Varambally Johanna M. Buschhaus Yu-Chih Chen Loredana Mauro Daniela Bonofiglio Alexey I. Nesvizhskii Gary D. Luker Sebastiano Andò Euisik Yoon Celina G. Kleer |
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hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis |
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A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis |
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Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance. |
abstractGer |
Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance. |
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Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance. |
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A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis |
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Maria E. Gonzalez Alessandro Paolì Ahmad Eido Yehyun Choi Boris Burman Sabra Djomehri Santhosh Kumar Karthikeyan Sooryanarayana Varambally Johanna M. Buschhaus Yu-Chih Chen Loredana Mauro Daniela Bonofiglio Alexey I. Nesvizhskii Gary D. Luker Sebastiano Andò Euisik Yoon Celina G. Kleer |
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The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. 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