Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-kappaB pathway.-猫眼课题宝

DOI：

10.3892/or_00000909

发表时间：

2010-09

期刊：

Oncology reports

影响因子：

4.2

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Feng Wu;Ye Yuan;Dong Li;Z. Lei;Chuanwang Song;Yanyan Liu;Bo Li;Bo Huang;Zuo-hua Feng;Gui-mei Zhang

T细胞免疫球蛋白和粘蛋白结构域3（Tim-3）最初被认为是Th 1细胞的受体。我们发现肿瘤细胞释放的TLR 4配体刺激内皮细胞后，Tim-3可以在内皮细胞中表达。内皮细胞表达的Tim-3不作为半乳糖凝集素-9的受体发挥作用，但介导内皮细胞与肿瘤细胞的相互作用。内皮细胞表达的Tim-3与B16黑色素瘤细胞上的非半乳糖凝集素9推定受体的结合可以触发B16细胞中的NF-κ B信号通路。活化的NF-κ B不仅促进B16细胞增殖，而且通过上调Bcl-2和Bcl-xL，下调Bax，增强B16细胞的抗凋亡能力。因此，Tim-3促进了B16细胞在血流中的存活，在肺中被阻止，并且在侵袭后，导致肺中更多的转移性结节。这些发现表明内皮细胞表达的Tim-3通过促进肿瘤细胞的内渗、在血流中的存活和外渗来增加肿瘤细胞的转移潜能。因此，抗炎或阻断Tim-3可能有助于预防转移。

T cell immunoglobulin and mucin domain-3 (Tim-3) is originally recognized as a receptor of Th1 cells. We found that Tim-3 could be expressed in endothelial cells after stimulation with tumor cell-released TLR4 ligand. Tim-3 expressed by endothelial cells does not function as the receptor of galectin-9, but mediates the interaction of endothelial cells with tumor cells. The engagement of endothelial cell-expressed Tim-3 with a non-galectin 9 putative receptor on B16 melanoma cells could trigger the NF-kappaB signaling pathway in B16 cells. The activated NF-kappaB not only promoted the proliferation of B16 cells, but also enhanced apoptosis resistance of B16 cells by up-regulating Bcl-2 and Bcl-xL and down-regulating Bax. Consistently, Tim-3 facilitated the survival of B16 cells in the blood stream, arrested in the lung and following invasion, resulted in more metastatic nodules in the lung. These findings suggest that endothelial cell-expressed Tim-3 increases tumor cell metastatic potential by facilitating tumor cell intravasation, survival in blood stream and extravasation. Thus, anti-inflammation or blockade of Tim-3 may contribute to the prevention of metastasis.

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-kappaB pathway.

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