CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages
Identifieur interne : 000986 ( Main/Exploration ); précédent : 000985; suivant : 000987CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages
Auteurs : Zihui Yang [République populaire de Chine] ; Huan Li [République populaire de Chine] ; Weiqi Wang [République populaire de Chine] ; Jianying Zhang [République populaire de Chine] ; Sen Jia [République populaire de Chine] ; Jun Wang [République populaire de Chine] ; Jianhua Wei [République populaire de Chine] ; Delin Lei [République populaire de Chine] ; Kaijin Hu [République populaire de Chine] ; Xinjie Yang [République populaire de Chine]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2019.
Abstract
Url:
DOI: 10.3389/fonc.2019.00231
PubMed: 31024838
PubMed Central: 6465613
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages</title><author><name sortKey="Yang, Zihui" sort="Yang, Zihui" uniqKey="Yang Z" first="Zihui" last="Yang">Zihui Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Huan" sort="Li, Huan" uniqKey="Li H" first="Huan" last="Li">Huan Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weiqi" sort="Wang, Weiqi" uniqKey="Wang W" first="Weiqi" last="Wang">Weiqi Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Jianying" sort="Zhang, Jianying" uniqKey="Zhang J" first="Jianying" last="Zhang">Jianying Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Sen" sort="Jia, Sen" uniqKey="Jia S" first="Sen" last="Jia">Sen Jia</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oral and Maxillofacial Surgery, Xi'an Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wei, Jianhua" sort="Wei, Jianhua" uniqKey="Wei J" first="Jianhua" last="Wei">Jianhua Wei</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Delin" sort="Lei, Delin" uniqKey="Lei D" first="Delin" last="Lei">Delin Lei</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hu, Kaijin" sort="Hu, Kaijin" uniqKey="Hu K" first="Kaijin" last="Hu">Kaijin Hu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Xinjie" sort="Yang, Xinjie" uniqKey="Yang X" first="Xinjie" last="Yang">Xinjie Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31024838</idno><idno type="pmc">6465613</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465613</idno><idno type="RBID">PMC:6465613</idno><idno type="doi">10.3389/fonc.2019.00231</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000559</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000559</idno><idno type="wicri:Area/Pmc/Curation">000559</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000559</idno><idno type="wicri:Area/Pmc/Checkpoint">000922</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000922</idno><idno type="wicri:Area/Ncbi/Merge">000567</idno><idno type="wicri:Area/Ncbi/Curation">000567</idno><idno type="wicri:Area/Ncbi/Checkpoint">000567</idno><idno type="wicri:Area/Main/Merge">000986</idno><idno type="wicri:Area/Main/Curation">000986</idno><idno type="wicri:Area/Main/Exploration">000986</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages</title><author><name sortKey="Yang, Zihui" sort="Yang, Zihui" uniqKey="Yang Z" first="Zihui" last="Yang">Zihui Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Huan" sort="Li, Huan" uniqKey="Li H" first="Huan" last="Li">Huan Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Weiqi" sort="Wang, Weiqi" uniqKey="Wang W" first="Weiqi" last="Wang">Weiqi Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Jianying" sort="Zhang, Jianying" uniqKey="Zhang J" first="Jianying" last="Zhang">Jianying Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Sen" sort="Jia, Sen" uniqKey="Jia S" first="Sen" last="Jia">Sen Jia</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oral and Maxillofacial Surgery, Xi'an Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wei, Jianhua" sort="Wei, Jianhua" uniqKey="Wei J" first="Jianhua" last="Wei">Jianhua Wei</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Delin" sort="Lei, Delin" uniqKey="Lei D" first="Delin" last="Lei">Delin Lei</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hu, Kaijin" sort="Hu, Kaijin" uniqKey="Hu K" first="Kaijin" last="Hu">Kaijin Hu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Xinjie" sort="Yang, Xinjie" uniqKey="Yang X" first="Xinjie" last="Yang">Xinjie Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University</institution>,<addr-line>Xi'an</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Oncology</title><idno type="eISSN">2234-943X</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Objective:</bold> The present study investigated the roles and underlying mechanism of CCL2/CCR2 axis in the interactions between tumor cells and tumor-associated macrophages (TAMs) during the progression of salivary adenoid cystic carcinoma (SACC).</p><p><bold>Methods:</bold> Immunohistochemical staining and survival analysis were performed to study the correlation and clinical value of CD68, CD163, CCL2, and CCR2 expression in SACC cases. CCL2 silencing by RNA interference and CCR2 blocking by CCR2 specific antagonist (RS504393) were performed. ELISA, qRT-PCR, western blot, immunofluorescence, flow cytometry, CCK8, scratch wound healing, and transwell assays were used to explore the functional roles and possible mechanism of CCL2/CCR2 axis in the interactions between SACC cells and TAMs. The effects of targeting TAMs by blocking the CCL2/CCR2 axis were investigated in a xenograft mice model with SACC cells.</p><p><bold>Results:</bold> The high infiltration of TAMs marked by CD68 and high infiltration of M2 TAMs marked by CD163 were significantly correlated with the expression of CCL2 and CCR2 in SACC tissues. Notably, the high infiltration of TAMs and the overexpression of CCL2 were obviously associated with the clinical progression and poor prognosis of SACC. SACC cells derived CCL2 could activate its receptor CCR2 expression in TAMs <italic>in vitro</italic>. The <italic>in vitro</italic> results further indicated that the SACC cells derived CCL2 was involved in the recruitment, M2 polarization, and GDNF expression of TAMs through the CCL2/CCR2 axis. Meanwhile, TAMs derived GDNF promoted the proliferation, migration, and invasion of SACC cells through the GDNF/p-RET pathway. Treating immunodeficient mice with the CCR2 antagonist (RS504393) greatly inhibited the infiltration of TAMs and the tumorigenicity of SACC cells.</p><p><bold>Conclusion:</bold> These new findings indicated that the CCL2/CCR2 axis promoted the progression of SACC cells via recruiting and reprogramming TAMs. Targeting TAMs by blocking the CCL2/CCR2 axis might be a prospective strategy for SACC therapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ganly, I" uniqKey="Ganly I">I Ganly</name></author><author><name sortKey="Amit, M" uniqKey="Amit M">M Amit</name></author><author><name sortKey="Kou, L" uniqKey="Kou L">L Kou</name></author><author><name sortKey="Palmer, Fl" uniqKey="Palmer F">FL Palmer</name></author><author><name sortKey="Migliacci, J" uniqKey="Migliacci J">J Migliacci</name></author><author><name sortKey="Katabi, N" uniqKey="Katabi N">N Katabi</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Sen" uniqKey="Jia S" first="Sen" last="Jia">Sen Jia</name><name sortKey="Lei, Delin" sort="Lei, Delin" uniqKey="Lei D" first="Delin" last="Lei">Delin Lei</name><name sortKey="Li, Huan" sort="Li, Huan" uniqKey="Li H" first="Huan" last="Li">Huan Li</name><name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name><name sortKey="Wang, Weiqi" sort="Wang, Weiqi" uniqKey="Wang W" first="Weiqi" last="Wang">Weiqi Wang</name><name sortKey="Wei, Jianhua" sort="Wei, Jianhua" uniqKey="Wei J" first="Jianhua" last="Wei">Jianhua Wei</name><name sortKey="Yang, Xinjie" sort="Yang, Xinjie" uniqKey="Yang X" first="Xinjie" last="Yang">Xinjie Yang</name><name sortKey="Zhang, Jianying" sort="Zhang, Jianying" uniqKey="Zhang J" first="Jianying" last="Zhang">Jianying Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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