Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers
Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor ( Procr ) as a surface marker on mammary stem...
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| Veröffentlicht in: | Cell research 2019-10, Vol.29 (10), p.832-845 |
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| creator | Wang, Daisong Hu, Xin Liu, Chunye Jia, Yingying Bai, Yiqin Cai, Cheguo Wang, Jingqiang Bai, Lanyue Yang, Ruikai Lin, ChangDong Liu, Yi-Rong Li, Shan Qiao, Feng Yao, Ling Chen, Li Ge, Gaoxiang Jiang, Hai Li, Dianfan Li, Lin Chen, JianFeng Shao, Zhi-Ming Zeng, Yi Arial |
| description | Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified
protein C receptor
(
Procr
) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of
Procr
in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr
+
cells are enriched for cancer stem cells (CSCs) in
Wnt1
basal-like tumors, but not in
Brca1
basal-like tumors or
PyVT
luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR
+
TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype. |
| doi_str_mv | 10.1038/s41422-019-0225-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6796873</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2284566425</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-3fe54448ad65014ef43fc2b913c607b53ecc0bfbb7f779389edfc4acf34c0eae3</originalsourceid><addsrcrecordid>eNp1kUuLVDEQhYMozjj6A9xIwI2bq5V37kaQxhcM6EI3bkJuutKTofvmmuQO-O9N0-P4AFcVqK9O1ckh5CmDlwyEfVUlk5wPwMYBOFfDeI-cMyPtYKyw9_sbgA2ggZ-RR7VeA3AlFXtIzgSTlhkN5-Tb55IbppluaMGAS8uFpko9bVdY_IJrS4HWhgcacL-nzZcdNtp5T7eptjSHRnclrwvNkU4FfW00-DlgqY_Jg-j3FZ_c1gvy9d3bL5sPw-Wn9x83by6HIA20QURUUkrrt1oBkxiliIFPIxNBg5mUwBBgitNkojGjsCNuY5A-RCEDoEdxQV6fdJd1OuA24NyK37ulpIMvP1z2yf3dmdOV2-Ubp82orRFd4MWtQMnfV6zNHVI92vUz5rU6zq1UWkuuOvr8H_Q6r2Xu9hwX_bfVaLXpFDtRoeRaC8a7Yxi4Y3LulJzrybljcm7sM8_-dHE38SuqDvATUHtr3mH5vfr_qj8BZtqlNA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2300159867</pqid></control><display><type>article</type><title>Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Wang, Daisong ; Hu, Xin ; Liu, Chunye ; Jia, Yingying ; Bai, Yiqin ; Cai, Cheguo ; Wang, Jingqiang ; Bai, Lanyue ; Yang, Ruikai ; Lin, ChangDong ; Liu, Yi-Rong ; Li, Shan ; Qiao, Feng ; Yao, Ling ; Chen, Li ; Ge, Gaoxiang ; Jiang, Hai ; Li, Dianfan ; Li, Lin ; Chen, JianFeng ; Shao, Zhi-Ming ; Zeng, Yi Arial</creator><creatorcontrib>Wang, Daisong ; Hu, Xin ; Liu, Chunye ; Jia, Yingying ; Bai, Yiqin ; Cai, Cheguo ; Wang, Jingqiang ; Bai, Lanyue ; Yang, Ruikai ; Lin, ChangDong ; Liu, Yi-Rong ; Li, Shan ; Qiao, Feng ; Yao, Ling ; Chen, Li ; Ge, Gaoxiang ; Jiang, Hai ; Li, Dianfan ; Li, Lin ; Chen, JianFeng ; Shao, Zhi-Ming ; Zeng, Yi Arial</creatorcontrib><description>Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified
protein C receptor
(
Procr
) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of
Procr
in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr
+
cells are enriched for cancer stem cells (CSCs) in
Wnt1
basal-like tumors, but not in
Brca1
basal-like tumors or
PyVT
luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR
+
TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.</description><identifier>ISSN: 1001-0602</identifier><identifier>EISSN: 1748-7838</identifier><identifier>DOI: 10.1038/s41422-019-0225-9</identifier><identifier>PMID: 31481760</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 13/105 ; 13/31 ; 14/1 ; 14/19 ; 631/532/71 ; 631/67/1347 ; Animals ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; BRCA1 protein ; BRCA1 Protein - genetics ; BRCA1 Protein - metabolism ; Breast cancer ; Cell Biology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Endothelial Protein C Receptor - antagonists & inhibitors ; Endothelial Protein C Receptor - genetics ; Endothelial Protein C Receptor - metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Life Sciences ; Mammary gland ; Mammary glands ; Mice ; Mice, Nude ; Mice, SCID ; Mutation ; Nanobodies ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - metabolism ; Protein C ; Proteins ; RNA Interference ; RNA, Small Interfering - metabolism ; Single-Domain Antibodies - immunology ; Single-Domain Antibodies - pharmacology ; Stem cell transplantation ; Stem cells ; Subgroups ; Surface markers ; Triple Negative Breast Neoplasms - metabolism ; Triple Negative Breast Neoplasms - mortality ; Triple Negative Breast Neoplasms - pathology ; Tumorigenesis ; Tumors ; Xenografts ; Xenotransplantation</subject><ispartof>Cell research, 2019-10, Vol.29 (10), p.832-845</ispartof><rights>IBCB, SIBS, CAS 2019</rights><rights>Copyright Nature Publishing Group Oct 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-3fe54448ad65014ef43fc2b913c607b53ecc0bfbb7f779389edfc4acf34c0eae3</citedby><cites>FETCH-LOGICAL-c470t-3fe54448ad65014ef43fc2b913c607b53ecc0bfbb7f779389edfc4acf34c0eae3</cites><orcidid>0000-0002-3821-7147 ; 0000-0003-4729-4678 ; 0000-0002-2508-5413 ; 0000-0003-1898-8099</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796873/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796873/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31481760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Daisong</creatorcontrib><creatorcontrib>Hu, Xin</creatorcontrib><creatorcontrib>Liu, Chunye</creatorcontrib><creatorcontrib>Jia, Yingying</creatorcontrib><creatorcontrib>Bai, Yiqin</creatorcontrib><creatorcontrib>Cai, Cheguo</creatorcontrib><creatorcontrib>Wang, Jingqiang</creatorcontrib><creatorcontrib>Bai, Lanyue</creatorcontrib><creatorcontrib>Yang, Ruikai</creatorcontrib><creatorcontrib>Lin, ChangDong</creatorcontrib><creatorcontrib>Liu, Yi-Rong</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Qiao, Feng</creatorcontrib><creatorcontrib>Yao, Ling</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Ge, Gaoxiang</creatorcontrib><creatorcontrib>Jiang, Hai</creatorcontrib><creatorcontrib>Li, Dianfan</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Chen, JianFeng</creatorcontrib><creatorcontrib>Shao, Zhi-Ming</creatorcontrib><creatorcontrib>Zeng, Yi Arial</creatorcontrib><title>Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers</title><title>Cell research</title><addtitle>Cell Res</addtitle><addtitle>Cell Res</addtitle><description>Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified
protein C receptor
(
Procr
) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of
Procr
in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr
+
cells are enriched for cancer stem cells (CSCs) in
Wnt1
basal-like tumors, but not in
Brca1
basal-like tumors or
PyVT
luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR
+
TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.</description><subject>13</subject><subject>13/100</subject><subject>13/105</subject><subject>13/31</subject><subject>14/1</subject><subject>14/19</subject><subject>631/532/71</subject><subject>631/67/1347</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>BRCA1 protein</subject><subject>BRCA1 Protein - genetics</subject><subject>BRCA1 Protein - metabolism</subject><subject>Breast cancer</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Endothelial Protein C Receptor - antagonists & inhibitors</subject><subject>Endothelial Protein C Receptor - genetics</subject><subject>Endothelial Protein C Receptor - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Life Sciences</subject><subject>Mammary gland</subject><subject>Mammary glands</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mice, SCID</subject><subject>Mutation</subject><subject>Nanobodies</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Protein C</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Single-Domain Antibodies - immunology</subject><subject>Single-Domain Antibodies - pharmacology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Subgroups</subject><subject>Surface markers</subject><subject>Triple Negative Breast Neoplasms - metabolism</subject><subject>Triple Negative Breast Neoplasms - mortality</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>1001-0602</issn><issn>1748-7838</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUuLVDEQhYMozjj6A9xIwI2bq5V37kaQxhcM6EI3bkJuutKTofvmmuQO-O9N0-P4AFcVqK9O1ckh5CmDlwyEfVUlk5wPwMYBOFfDeI-cMyPtYKyw9_sbgA2ggZ-RR7VeA3AlFXtIzgSTlhkN5-Tb55IbppluaMGAS8uFpko9bVdY_IJrS4HWhgcacL-nzZcdNtp5T7eptjSHRnclrwvNkU4FfW00-DlgqY_Jg-j3FZ_c1gvy9d3bL5sPw-Wn9x83by6HIA20QURUUkrrt1oBkxiliIFPIxNBg5mUwBBgitNkojGjsCNuY5A-RCEDoEdxQV6fdJd1OuA24NyK37ulpIMvP1z2yf3dmdOV2-Ubp82orRFd4MWtQMnfV6zNHVI92vUz5rU6zq1UWkuuOvr8H_Q6r2Xu9hwX_bfVaLXpFDtRoeRaC8a7Yxi4Y3LulJzrybljcm7sM8_-dHE38SuqDvATUHtr3mH5vfr_qj8BZtqlNA</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Wang, Daisong</creator><creator>Hu, Xin</creator><creator>Liu, Chunye</creator><creator>Jia, Yingying</creator><creator>Bai, Yiqin</creator><creator>Cai, Cheguo</creator><creator>Wang, Jingqiang</creator><creator>Bai, Lanyue</creator><creator>Yang, Ruikai</creator><creator>Lin, ChangDong</creator><creator>Liu, Yi-Rong</creator><creator>Li, Shan</creator><creator>Qiao, Feng</creator><creator>Yao, Ling</creator><creator>Chen, Li</creator><creator>Ge, Gaoxiang</creator><creator>Jiang, Hai</creator><creator>Li, Dianfan</creator><creator>Li, Lin</creator><creator>Chen, JianFeng</creator><creator>Shao, Zhi-Ming</creator><creator>Zeng, Yi Arial</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3821-7147</orcidid><orcidid>https://orcid.org/0000-0003-4729-4678</orcidid><orcidid>https://orcid.org/0000-0002-2508-5413</orcidid><orcidid>https://orcid.org/0000-0003-1898-8099</orcidid></search><sort><creationdate>20191001</creationdate><title>Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers</title><author>Wang, Daisong ; Hu, Xin ; Liu, Chunye ; Jia, Yingying ; Bai, Yiqin ; Cai, Cheguo ; Wang, Jingqiang ; Bai, Lanyue ; Yang, Ruikai ; Lin, ChangDong ; Liu, Yi-Rong ; Li, Shan ; Qiao, Feng ; Yao, Ling ; Chen, Li ; Ge, Gaoxiang ; Jiang, Hai ; Li, Dianfan ; Li, Lin ; Chen, JianFeng ; Shao, Zhi-Ming ; Zeng, Yi Arial</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-3fe54448ad65014ef43fc2b913c607b53ecc0bfbb7f779389edfc4acf34c0eae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13</topic><topic>13/100</topic><topic>13/105</topic><topic>13/31</topic><topic>14/1</topic><topic>14/19</topic><topic>631/532/71</topic><topic>631/67/1347</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>BRCA1 protein</topic><topic>BRCA1 Protein - genetics</topic><topic>BRCA1 Protein - metabolism</topic><topic>Breast cancer</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Endothelial Protein C Receptor - antagonists & inhibitors</topic><topic>Endothelial Protein C Receptor - genetics</topic><topic>Endothelial Protein C Receptor - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Life Sciences</topic><topic>Mammary gland</topic><topic>Mammary glands</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mice, SCID</topic><topic>Mutation</topic><topic>Nanobodies</topic><topic>Neoplastic Stem Cells - immunology</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Protein C</topic><topic>Proteins</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Single-Domain Antibodies - immunology</topic><topic>Single-Domain Antibodies - pharmacology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Subgroups</topic><topic>Surface markers</topic><topic>Triple Negative Breast Neoplasms - metabolism</topic><topic>Triple Negative Breast Neoplasms - mortality</topic><topic>Triple Negative Breast Neoplasms - pathology</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Daisong</creatorcontrib><creatorcontrib>Hu, Xin</creatorcontrib><creatorcontrib>Liu, Chunye</creatorcontrib><creatorcontrib>Jia, Yingying</creatorcontrib><creatorcontrib>Bai, Yiqin</creatorcontrib><creatorcontrib>Cai, Cheguo</creatorcontrib><creatorcontrib>Wang, Jingqiang</creatorcontrib><creatorcontrib>Bai, Lanyue</creatorcontrib><creatorcontrib>Yang, Ruikai</creatorcontrib><creatorcontrib>Lin, ChangDong</creatorcontrib><creatorcontrib>Liu, Yi-Rong</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Qiao, Feng</creatorcontrib><creatorcontrib>Yao, Ling</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Ge, Gaoxiang</creatorcontrib><creatorcontrib>Jiang, Hai</creatorcontrib><creatorcontrib>Li, Dianfan</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Chen, JianFeng</creatorcontrib><creatorcontrib>Shao, Zhi-Ming</creatorcontrib><creatorcontrib>Zeng, Yi Arial</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Daisong</au><au>Hu, Xin</au><au>Liu, Chunye</au><au>Jia, Yingying</au><au>Bai, Yiqin</au><au>Cai, Cheguo</au><au>Wang, Jingqiang</au><au>Bai, Lanyue</au><au>Yang, Ruikai</au><au>Lin, ChangDong</au><au>Liu, Yi-Rong</au><au>Li, Shan</au><au>Qiao, Feng</au><au>Yao, Ling</au><au>Chen, Li</au><au>Ge, Gaoxiang</au><au>Jiang, Hai</au><au>Li, Dianfan</au><au>Li, Lin</au><au>Chen, JianFeng</au><au>Shao, Zhi-Ming</au><au>Zeng, Yi Arial</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers</atitle><jtitle>Cell research</jtitle><stitle>Cell Res</stitle><addtitle>Cell Res</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>29</volume><issue>10</issue><spage>832</spage><epage>845</epage><pages>832-845</pages><issn>1001-0602</issn><eissn>1748-7838</eissn><abstract>Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified
protein C receptor
(
Procr
) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of
Procr
in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr
+
cells are enriched for cancer stem cells (CSCs) in
Wnt1
basal-like tumors, but not in
Brca1
basal-like tumors or
PyVT
luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR
+
TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31481760</pmid><doi>10.1038/s41422-019-0225-9</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-3821-7147</orcidid><orcidid>https://orcid.org/0000-0003-4729-4678</orcidid><orcidid>https://orcid.org/0000-0002-2508-5413</orcidid><orcidid>https://orcid.org/0000-0003-1898-8099</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell research, 2019-10, Vol.29 (10), p.832-845 |
| issn | 1001-0602 1748-7838 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6796873 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 13 13/100 13/105 13/31 14/1 14/19 631/532/71 631/67/1347 Animals Biomarkers Biomarkers, Tumor - metabolism Biomedical and Life Sciences BRCA1 protein BRCA1 Protein - genetics BRCA1 Protein - metabolism Breast cancer Cell Biology Cell Line, Tumor Cell Proliferation - drug effects Endothelial Protein C Receptor - antagonists & inhibitors Endothelial Protein C Receptor - genetics Endothelial Protein C Receptor - metabolism Female Humans Kaplan-Meier Estimate Life Sciences Mammary gland Mammary glands Mice Mice, Nude Mice, SCID Mutation Nanobodies Neoplastic Stem Cells - immunology Neoplastic Stem Cells - metabolism Protein C Proteins RNA Interference RNA, Small Interfering - metabolism Single-Domain Antibodies - immunology Single-Domain Antibodies - pharmacology Stem cell transplantation Stem cells Subgroups Surface markers Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - mortality Triple Negative Breast Neoplasms - pathology Tumorigenesis Tumors Xenografts Xenotransplantation |
| title | Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T21%3A39%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protein%20C%20receptor%20is%20a%20therapeutic%20stem%20cell%20target%20in%20a%20distinct%20group%20of%20breast%20cancers&rft.jtitle=Cell%20research&rft.au=Wang,%20Daisong&rft.date=2019-10-01&rft.volume=29&rft.issue=10&rft.spage=832&rft.epage=845&rft.pages=832-845&rft.issn=1001-0602&rft.eissn=1748-7838&rft_id=info:doi/10.1038/s41422-019-0225-9&rft_dat=%3Cproquest_pubme%3E2284566425%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2300159867&rft_id=info:pmid/31481760&rfr_iscdi=true |