Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy
Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immu...
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| Veröffentlicht in: | Clinical cancer research 2016-07, Vol.22 (13), p.3298-3309 |
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| creator | Morita, Rena Hirohashi, Yoshihiko Torigoe, Toshihiko Ito-Inoda, Satoko Takahashi, Akari Mariya, Tasuku Asanuma, Hiroko Tamura, Yasuaki Tsukahara, Tomohide Kanaseki, Takayuki Kubo, Terufumi Kutomi, Goro Mizuguchi, Toru Terui, Takeshi Ishitani, Kunihiko Hashino, Satoshi Kondo, Toru Minagawa, Nozomi Takahashi, Norihiko Taketomi, Akinobu Todo, Satoru Asaka, Masahiro Sato, Noriyuki |
| description | Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.
Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR. |
| doi_str_mv | 10.1158/1078-0432.CCR-15-1709 |
| format | Article |
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Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-15-1709</identifier><identifier>PMID: 26861454</identifier><language>eng</language><publisher>United States</publisher><subject>Adenocarcinoma - immunology ; Adenocarcinoma - pathology ; Adenocarcinoma - therapy ; Animals ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - immunology ; Colonic Neoplasms - immunology ; Colonic Neoplasms - pathology ; Colonic Neoplasms - therapy ; HT29 Cells ; Humans ; Immunotherapy - methods ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplastic Stem Cells - immunology ; Prognosis ; Receptors, Odorant - biosynthesis ; Receptors, Odorant - genetics ; Receptors, Odorant - immunology ; RNA Interference ; RNA, Small Interfering - genetics ; Spheroids, Cellular ; T-Lymphocytes, Cytotoxic - immunology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical cancer research, 2016-07, Vol.22 (13), p.3298-3309</ispartof><rights>2016 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-401eff9ba9d93347e151aaeb2a40c2f2f9b3cc23a0b77a2e128ea82045d905213</citedby><cites>FETCH-LOGICAL-c455t-401eff9ba9d93347e151aaeb2a40c2f2f9b3cc23a0b77a2e128ea82045d905213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26861454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morita, Rena</creatorcontrib><creatorcontrib>Hirohashi, Yoshihiko</creatorcontrib><creatorcontrib>Torigoe, Toshihiko</creatorcontrib><creatorcontrib>Ito-Inoda, Satoko</creatorcontrib><creatorcontrib>Takahashi, Akari</creatorcontrib><creatorcontrib>Mariya, Tasuku</creatorcontrib><creatorcontrib>Asanuma, Hiroko</creatorcontrib><creatorcontrib>Tamura, Yasuaki</creatorcontrib><creatorcontrib>Tsukahara, Tomohide</creatorcontrib><creatorcontrib>Kanaseki, Takayuki</creatorcontrib><creatorcontrib>Kubo, Terufumi</creatorcontrib><creatorcontrib>Kutomi, Goro</creatorcontrib><creatorcontrib>Mizuguchi, Toru</creatorcontrib><creatorcontrib>Terui, Takeshi</creatorcontrib><creatorcontrib>Ishitani, Kunihiko</creatorcontrib><creatorcontrib>Hashino, Satoshi</creatorcontrib><creatorcontrib>Kondo, Toru</creatorcontrib><creatorcontrib>Minagawa, Nozomi</creatorcontrib><creatorcontrib>Takahashi, Norihiko</creatorcontrib><creatorcontrib>Taketomi, Akinobu</creatorcontrib><creatorcontrib>Todo, Satoru</creatorcontrib><creatorcontrib>Asaka, Masahiro</creatorcontrib><creatorcontrib>Sato, Noriyuki</creatorcontrib><title>Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.
Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.</description><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - therapy</subject><subject>Animals</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - immunology</subject><subject>Colonic Neoplasms - immunology</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - therapy</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Immunotherapy - methods</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Prognosis</subject><subject>Receptors, Odorant - biosynthesis</subject><subject>Receptors, Odorant - genetics</subject><subject>Receptors, Odorant - immunology</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Spheroids, Cellular</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1TAQRi0Eon88AshLNmk9jp04SxRRuFJLq7asrYnvpASS-GI7SPcZ-tI4ui1rVv5kn88z0mHsPYhzAG0uQNSmEKqU5217V4AuoBbNK3YMWtdFKSv9OucX5oidxPhTCFAg1Ft2JCtTgdLqmD3djD265MOe35GjXU78Eqdh3POa3y9df8gtv6apo8CBbyJH_s3_oZFfY_iV73zPWz_6mbc4OwrFZh7SgGmYH3lL45j5eXuo3fpEc-IPGB4prb3NNC2zTz8o4G5_xt70OEZ693yesu-Xnx_ar8XVzZdN--mqcErrVCgB1PdNh822KUtVE2hApE6iEk72Mj-VzskSRVfXKAmkITRSKL1thJZQnrKPh393wf9eKCY7DdHlTXEmv0QLRpjKNMb8FwoqL1HVGdUH1AUfY6De7sIwYdhbEHZVZlcddtVhszIL2q7Kcu_D84ilm2j7r_XiqPwLt5-RJA</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Morita, Rena</creator><creator>Hirohashi, Yoshihiko</creator><creator>Torigoe, Toshihiko</creator><creator>Ito-Inoda, Satoko</creator><creator>Takahashi, Akari</creator><creator>Mariya, Tasuku</creator><creator>Asanuma, Hiroko</creator><creator>Tamura, Yasuaki</creator><creator>Tsukahara, Tomohide</creator><creator>Kanaseki, Takayuki</creator><creator>Kubo, Terufumi</creator><creator>Kutomi, Goro</creator><creator>Mizuguchi, Toru</creator><creator>Terui, Takeshi</creator><creator>Ishitani, Kunihiko</creator><creator>Hashino, Satoshi</creator><creator>Kondo, Toru</creator><creator>Minagawa, Nozomi</creator><creator>Takahashi, Norihiko</creator><creator>Taketomi, Akinobu</creator><creator>Todo, Satoru</creator><creator>Asaka, Masahiro</creator><creator>Sato, Noriyuki</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20160701</creationdate><title>Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy</title><author>Morita, Rena ; Hirohashi, Yoshihiko ; Torigoe, Toshihiko ; Ito-Inoda, Satoko ; Takahashi, Akari ; Mariya, Tasuku ; Asanuma, Hiroko ; Tamura, Yasuaki ; Tsukahara, Tomohide ; Kanaseki, Takayuki ; Kubo, Terufumi ; Kutomi, Goro ; Mizuguchi, Toru ; Terui, Takeshi ; Ishitani, Kunihiko ; Hashino, Satoshi ; Kondo, Toru ; Minagawa, Nozomi ; Takahashi, Norihiko ; Taketomi, Akinobu ; Todo, Satoru ; Asaka, Masahiro ; Sato, Noriyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-401eff9ba9d93347e151aaeb2a40c2f2f9b3cc23a0b77a2e128ea82045d905213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - therapy</topic><topic>Animals</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Colonic Neoplasms - immunology</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colonic Neoplasms - therapy</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Immunotherapy - methods</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Neoplastic Stem Cells - immunology</topic><topic>Prognosis</topic><topic>Receptors, Odorant - biosynthesis</topic><topic>Receptors, Odorant - genetics</topic><topic>Receptors, Odorant - immunology</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Spheroids, Cellular</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morita, Rena</creatorcontrib><creatorcontrib>Hirohashi, Yoshihiko</creatorcontrib><creatorcontrib>Torigoe, Toshihiko</creatorcontrib><creatorcontrib>Ito-Inoda, Satoko</creatorcontrib><creatorcontrib>Takahashi, Akari</creatorcontrib><creatorcontrib>Mariya, Tasuku</creatorcontrib><creatorcontrib>Asanuma, Hiroko</creatorcontrib><creatorcontrib>Tamura, Yasuaki</creatorcontrib><creatorcontrib>Tsukahara, Tomohide</creatorcontrib><creatorcontrib>Kanaseki, Takayuki</creatorcontrib><creatorcontrib>Kubo, Terufumi</creatorcontrib><creatorcontrib>Kutomi, Goro</creatorcontrib><creatorcontrib>Mizuguchi, Toru</creatorcontrib><creatorcontrib>Terui, Takeshi</creatorcontrib><creatorcontrib>Ishitani, Kunihiko</creatorcontrib><creatorcontrib>Hashino, Satoshi</creatorcontrib><creatorcontrib>Kondo, Toru</creatorcontrib><creatorcontrib>Minagawa, Nozomi</creatorcontrib><creatorcontrib>Takahashi, Norihiko</creatorcontrib><creatorcontrib>Taketomi, Akinobu</creatorcontrib><creatorcontrib>Todo, Satoru</creatorcontrib><creatorcontrib>Asaka, Masahiro</creatorcontrib><creatorcontrib>Sato, Noriyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morita, Rena</au><au>Hirohashi, Yoshihiko</au><au>Torigoe, Toshihiko</au><au>Ito-Inoda, Satoko</au><au>Takahashi, Akari</au><au>Mariya, Tasuku</au><au>Asanuma, Hiroko</au><au>Tamura, Yasuaki</au><au>Tsukahara, Tomohide</au><au>Kanaseki, Takayuki</au><au>Kubo, Terufumi</au><au>Kutomi, Goro</au><au>Mizuguchi, Toru</au><au>Terui, Takeshi</au><au>Ishitani, Kunihiko</au><au>Hashino, Satoshi</au><au>Kondo, Toru</au><au>Minagawa, Nozomi</au><au>Takahashi, Norihiko</au><au>Taketomi, Akinobu</au><au>Todo, Satoru</au><au>Asaka, Masahiro</au><au>Sato, Noriyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>22</volume><issue>13</issue><spage>3298</spage><epage>3309</epage><pages>3298-3309</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.
Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.</abstract><cop>United States</cop><pmid>26861454</pmid><doi>10.1158/1078-0432.CCR-15-1709</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2016-07, Vol.22 (13), p.3298-3309 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - immunology Adenocarcinoma - pathology Adenocarcinoma - therapy Animals Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Biomarkers, Tumor - immunology Colonic Neoplasms - immunology Colonic Neoplasms - pathology Colonic Neoplasms - therapy HT29 Cells Humans Immunotherapy - methods Mice Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells - immunology Prognosis Receptors, Odorant - biosynthesis Receptors, Odorant - genetics Receptors, Odorant - immunology RNA Interference RNA, Small Interfering - genetics Spheroids, Cellular T-Lymphocytes, Cytotoxic - immunology Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title | Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy |
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