PI3Ka activates integrin α4?1 to establish a metastatic niche in lymph nodes

Garmy-Susini B.; Avraamides C.J.; Desgrosellier J.S.Schmid M.C.Foubert P.Ellies L.G.Lowy A.M.Blair S.L.Vandenberg S.R.Datnow B.Wang H.-Y.Cheresh D.A.Varner J.

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PI3Ka activates integrin α4?1 to establish a metastatic niche in lymph nodes

机译：PI3Ka activates integrin α4?1 to establish a metastatic niche in lymph nodes

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Lymph nodes are initial sites of tumor metastasis, yet whether the lymph node microenvironment actively promotes tumor metastasis remains unknown. We show here that VEGF-C/PI3Ka-driven remodeling of lymph nodes promotes tumor metastasis by activating integrin α4?1 on lymph node lymphatic endothelium. Activated integrin α4?1 promotes expansion of the lymphatic endothelium in lymph nodes and serves as an adhesive ligand that captures vascular cell adhesion molecule 1 (VCAM-1)+ metastatic tumor cells, thereby promoting lymph node metastasis. Experimental induction of α4?1 expression in lymph nodes is sufficient to promote tumor cell adhesion to lymphatic endothelium and lymph node metastasis in vivo, whereas genetic or pharmacological blockade of integrin α4?1 or VCAM-1 inhibits it. As lymph node metastases accurately predict poor disease outcome, and integrin α4?1 is a biomarker of lymphatic endothelium in tumor-draining lymph nodes from animals and patients, these results indicate that targeting integrin α4?1 or VCAM to inhibit the interactions of tumor cells with the lymph node microenvironment may be an effective strategy to suppress tumor metastasis.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第22期|9042-9047|共6页
作者
Garmy-Susini B.; Avraamides C.J.; Desgrosellier J.S.Schmid M.C.Foubert P.Ellies L.G.Lowy A.M.Blair S.L.Vandenberg S.R.Datnow B.Wang H.-Y.Cheresh D.A.Varner J.;
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Moores Cancer Center, University of California, San Diego, CA 92093-0819, United States;

Departments of Pathology, University of California, San Diego, CA 92093-0819, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
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PI3Ka activates integrin α4?1 to establish a metastatic niche in lymph nodes

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