sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS
Identifieur interne : 000882 ( Main/Exploration ); précédent : 000881; suivant : 000883sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS
Auteurs : Yan Zou [République populaire de Chine] ; Fengxian Qin [République populaire de Chine] ; Jifei Chen [République populaire de Chine] ; Jie Meng [République populaire de Chine] ; Liuhua Wei [République populaire de Chine] ; Chunlin Wu [République populaire de Chine] ; Qiaoyun Zhang [République populaire de Chine] ; Dong Wei [République populaire de Chine] ; Xiang Chen [République populaire de Chine] ; Hao Wu [République populaire de Chine] ; Xiaoli Chen [République populaire de Chine] ; Shengming Dai [République populaire de Chine]Source :
- Oncotarget [ 1949-2553 ] ; 2016.
Abstract
Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD-2 complex could inhibit CRC by competing with binding LPS, raising the complex's possibility of a new prevention agent against CRC.
Url:
DOI: 10.18632/oncotarget.10496
PubMed: 27409669
PubMed Central: 5239533
Affiliations:
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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Qin, Fengxian" sort="Qin, Fengxian" uniqKey="Qin F" first="Fengxian" last="Qin">Fengxian Qin</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Jifei" sort="Chen, Jifei" uniqKey="Chen J" first="Jifei" last="Chen">Jifei Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Meng, Jie" sort="Meng, Jie" uniqKey="Meng J" first="Jie" last="Meng">Jie Meng</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Liuhua" sort="Wei, Liuhua" uniqKey="Wei L" first="Liuhua" last="Wei">Liuhua Wei</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Chunlin" sort="Wu, Chunlin" uniqKey="Wu C" first="Chunlin" last="Wu">Chunlin Wu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Qiaoyun" sort="Zhang, Qiaoyun" uniqKey="Zhang Q" first="Qiaoyun" last="Zhang">Qiaoyun Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Dong" sort="Wei, Dong" uniqKey="Wei D" first="Dong" last="Wei">Dong Wei</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xiang" sort="Chen, Xiang" uniqKey="Chen X" first="Xiang" last="Chen">Xiang Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xiaoli" sort="Chen, Xiaoli" uniqKey="Chen X" first="Xiaoli" last="Chen">Xiaoli Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author><author><name sortKey="Dai, Shengming" sort="Dai, Shengming" uniqKey="Dai S" first="Shengming" last="Dai">Shengming Dai</name><affiliation wicri:level="1"><nlm:aff id="A1"> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea> Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005</wicri:regionArea><wicri:noRegion>545005</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD-2 complex could inhibit CRC by competing with binding LPS, raising the complex's possibility of a new prevention agent against CRC.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chen, W" uniqKey="Chen W">W Chen</name></author><author><name sortKey="Zheng, R" uniqKey="Zheng R">R Zheng</name></author><author><name sortKey="Zeng, H" uniqKey="Zeng H">H Zeng</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="He, J" uniqKey="He J">J He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balkwill, F" uniqKey="Balkwill F">F Balkwill</name></author><author><name sortKey="Coussens, Lm" uniqKey="Coussens L">LM Coussens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelly, Mg" uniqKey="Kelly M">MG Kelly</name></author><author><name sortKey="Alvero, Ab" uniqKey="Alvero 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Jie" sort="Meng, Jie" uniqKey="Meng J" first="Jie" last="Meng">Jie Meng</name><name sortKey="Qin, Fengxian" sort="Qin, Fengxian" uniqKey="Qin F" first="Fengxian" last="Qin">Fengxian Qin</name><name sortKey="Wei, Dong" sort="Wei, Dong" uniqKey="Wei D" first="Dong" last="Wei">Dong Wei</name><name sortKey="Wei, Liuhua" sort="Wei, Liuhua" uniqKey="Wei L" first="Liuhua" last="Wei">Liuhua Wei</name><name sortKey="Wu, Chunlin" sort="Wu, Chunlin" uniqKey="Wu C" first="Chunlin" last="Wu">Chunlin Wu</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><name sortKey="Zhang, Qiaoyun" sort="Zhang, Qiaoyun" uniqKey="Zhang Q" first="Qiaoyun" last="Zhang">Qiaoyun Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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