Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo

A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely co...
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Autor*in:	Alyssa D. Merting [verfasserIn] Dakota B. Poschel [verfasserIn] Chunwan Lu [verfasserIn] John D. Klement [verfasserIn] Dafeng Yang [verfasserIn] Honglin Li [verfasserIn] Huidong Shi [verfasserIn] Eric Chapdelaine [verfasserIn] Mitzi Montgomery [verfasserIn] Michael T. Redman [verfasserIn] Natasha M. Savage [verfasserIn] Asha Nayak-Kapoor [verfasserIn] Kebin Liu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 14(2022), 2, p 361
Übergeordnetes Werk:	volume:14 ; year:2022 ; number:2, p 361

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers14020361

Katalog-ID:	DOAJ074706063

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allfields	10.3390/cancers14020361 doi (DE-627)DOAJ074706063 (DE-599)DOAJd7f5d7edcbaf4f48af54f4587ad62730 DE-627 ger DE-627 rakwb eng RC254-282 Alyssa D. Merting verfasserin aut Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo. FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dakota B. Poschel verfasserin aut Chunwan Lu verfasserin aut John D. Klement verfasserin aut Dafeng Yang verfasserin aut Honglin Li verfasserin aut Huidong Shi verfasserin aut Eric Chapdelaine verfasserin aut Mitzi Montgomery verfasserin aut Michael T. Redman verfasserin aut Natasha M. Savage verfasserin aut Asha Nayak-Kapoor verfasserin aut Kebin Liu verfasserin aut In Cancers MDPI AG, 2010 14(2022), 2, p 361 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:2, p 361 https://doi.org/10.3390/cancers14020361 kostenfrei https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 kostenfrei https://www.mdpi.com/2072-6694/14/2/361 kostenfrei https://doaj.org/toc/2072-6694 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_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 14 2022 2, p 361
spelling	10.3390/cancers14020361 doi (DE-627)DOAJ074706063 (DE-599)DOAJd7f5d7edcbaf4f48af54f4587ad62730 DE-627 ger DE-627 rakwb eng RC254-282 Alyssa D. Merting verfasserin aut Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo. FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dakota B. Poschel verfasserin aut Chunwan Lu verfasserin aut John D. Klement verfasserin aut Dafeng Yang verfasserin aut Honglin Li verfasserin aut Huidong Shi verfasserin aut Eric Chapdelaine verfasserin aut Mitzi Montgomery verfasserin aut Michael T. Redman verfasserin aut Natasha M. Savage verfasserin aut Asha Nayak-Kapoor verfasserin aut Kebin Liu verfasserin aut In Cancers MDPI AG, 2010 14(2022), 2, p 361 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:2, p 361 https://doi.org/10.3390/cancers14020361 kostenfrei https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 kostenfrei https://www.mdpi.com/2072-6694/14/2/361 kostenfrei https://doaj.org/toc/2072-6694 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_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 14 2022 2, p 361
allfields_unstemmed	10.3390/cancers14020361 doi (DE-627)DOAJ074706063 (DE-599)DOAJd7f5d7edcbaf4f48af54f4587ad62730 DE-627 ger DE-627 rakwb eng RC254-282 Alyssa D. Merting verfasserin aut Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo. FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dakota B. Poschel verfasserin aut Chunwan Lu verfasserin aut John D. Klement verfasserin aut Dafeng Yang verfasserin aut Honglin Li verfasserin aut Huidong Shi verfasserin aut Eric Chapdelaine verfasserin aut Mitzi Montgomery verfasserin aut Michael T. Redman verfasserin aut Natasha M. Savage verfasserin aut Asha Nayak-Kapoor verfasserin aut Kebin Liu verfasserin aut In Cancers MDPI AG, 2010 14(2022), 2, p 361 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:2, p 361 https://doi.org/10.3390/cancers14020361 kostenfrei https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 kostenfrei https://www.mdpi.com/2072-6694/14/2/361 kostenfrei https://doaj.org/toc/2072-6694 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_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 14 2022 2, p 361
allfieldsGer	10.3390/cancers14020361 doi (DE-627)DOAJ074706063 (DE-599)DOAJd7f5d7edcbaf4f48af54f4587ad62730 DE-627 ger DE-627 rakwb eng RC254-282 Alyssa D. Merting verfasserin aut Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo. FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dakota B. Poschel verfasserin aut Chunwan Lu verfasserin aut John D. Klement verfasserin aut Dafeng Yang verfasserin aut Honglin Li verfasserin aut Huidong Shi verfasserin aut Eric Chapdelaine verfasserin aut Mitzi Montgomery verfasserin aut Michael T. Redman verfasserin aut Natasha M. Savage verfasserin aut Asha Nayak-Kapoor verfasserin aut Kebin Liu verfasserin aut In Cancers MDPI AG, 2010 14(2022), 2, p 361 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:2, p 361 https://doi.org/10.3390/cancers14020361 kostenfrei https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 kostenfrei https://www.mdpi.com/2072-6694/14/2/361 kostenfrei https://doaj.org/toc/2072-6694 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_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 14 2022 2, p 361
allfieldsSound	10.3390/cancers14020361 doi (DE-627)DOAJ074706063 (DE-599)DOAJd7f5d7edcbaf4f48af54f4587ad62730 DE-627 ger DE-627 rakwb eng RC254-282 Alyssa D. Merting verfasserin aut Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo. FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dakota B. Poschel verfasserin aut Chunwan Lu verfasserin aut John D. Klement verfasserin aut Dafeng Yang verfasserin aut Honglin Li verfasserin aut Huidong Shi verfasserin aut Eric Chapdelaine verfasserin aut Mitzi Montgomery verfasserin aut Michael T. Redman verfasserin aut Natasha M. Savage verfasserin aut Asha Nayak-Kapoor verfasserin aut Kebin Liu verfasserin aut In Cancers MDPI AG, 2010 14(2022), 2, p 361 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:2, p 361 https://doi.org/10.3390/cancers14020361 kostenfrei https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 kostenfrei https://www.mdpi.com/2072-6694/14/2/361 kostenfrei https://doaj.org/toc/2072-6694 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_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 14 2022 2, p 361
language	English
source	In Cancers 14(2022), 2, p 361 volume:14 year:2022 number:2, p 361
sourceStr	In Cancers 14(2022), 2, p 361 volume:14 year:2022 number:2, p 361
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Alyssa D. Merting @@aut@@ Dakota B. Poschel @@aut@@ Chunwan Lu @@aut@@ John D. Klement @@aut@@ Dafeng Yang @@aut@@ Honglin Li @@aut@@ Huidong Shi @@aut@@ Eric Chapdelaine @@aut@@ Mitzi Montgomery @@aut@@ Michael T. Redman @@aut@@ Natasha M. Savage @@aut@@ Asha Nayak-Kapoor @@aut@@ Kebin Liu @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ074706063
language_de	englisch
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callnumber-first	R - Medicine
author	Alyssa D. Merting
spellingShingle	Alyssa D. Merting misc RC254-282 misc FAS misc colon cancer misc metastasis misc cytotoxic T lymphocyte misc cationic lipid nanoparticle misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo
authorStr	Alyssa D. Merting
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topic_title	RC254-282 Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo FAS colon cancer metastasis cytotoxic T lymphocyte cationic lipid nanoparticle
topic	misc RC254-282 misc FAS misc colon cancer misc metastasis misc cytotoxic T lymphocyte misc cationic lipid nanoparticle misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc FAS misc colon cancer misc metastasis misc cytotoxic T lymphocyte misc cationic lipid nanoparticle misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc FAS misc colon cancer misc metastasis misc cytotoxic T lymphocyte misc cationic lipid nanoparticle misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo
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title_full	Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo
author_sort	Alyssa D. Merting
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author_browse	Alyssa D. Merting Dakota B. Poschel Chunwan Lu John D. Klement Dafeng Yang Honglin Li Huidong Shi Eric Chapdelaine Mitzi Montgomery Michael T. Redman Natasha M. Savage Asha Nayak-Kapoor Kebin Liu
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title_sort	restoring fas expression via lipid-encapsulated fas dna nanoparticle delivery is sufficient to suppress colon tumor growth in vivo
callnumber	RC254-282
title_auth	Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo
abstract	A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo.
abstractGer	A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo.
abstract_unstemmed	A hallmark of human colorectal cancer is lost expression of FAS, the death receptor for FASL of cytotoxic T lymphocytes (CTLs). However, it is unknown whether restoring FAS expression alone is sufficient to suppress csolorectal-cancer development. The FAS promoter is hypermethylated and inversely correlated with FAS mRNA level in human colorectal carcinomas. Analysis of single-cell RNA-Seq datasets revealed that FAS is highly expressed in epithelial cells and immune cells but down-regulated in colon-tumor cells in human colorectal-cancer patients. Codon usage-optimized mouse and human FAS cDNA was designed, synthesized, and encapsulated into cationic lipid to formulate nanoparticle DOTAP-Chol-mFAS and DOTAP-Chol-hFAS, respectively. Overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS<sup<+</sup< tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo. Overexpression of codon-optimized FAS-induced FAS receptor auto-oligomerization and tumor cell auto-apoptosis in metastatic human colon-tumor cells. DOTAP-Chol-hFAS therapy is also sufficient to suppress metastatic human colon tumor xenograft growth in athymic mice. DOTAP-Chol-mFAS therapy exhibited no significant liver toxicity. Our data determined that tumor-selective delivery of FAS DNA nanoparticles is sufficient for suppression of human colon tumor growth in vivo.
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title_short	Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo
url	https://doi.org/10.3390/cancers14020361 https://doaj.org/article/d7f5d7edcbaf4f48af54f4587ad62730 https://www.mdpi.com/2072-6694/14/2/361 https://doaj.org/toc/2072-6694
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author2	Dakota B. Poschel Chunwan Lu John D. Klement Dafeng Yang Honglin Li Huidong Shi Eric Chapdelaine Mitzi Montgomery Michael T. Redman Natasha M. Savage Asha Nayak-Kapoor Kebin Liu
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