Laminin‐421 produced by lymphatic endothelial cells induces chemotaxis for human melanoma cells
Laminin‐421 produced by lymphatic endothelial cells induces chemotaxis for human melanoma cells
复制标题
DOI：
10.1111/j.1755-148x.2009.00590.x
复制
发表时间：
2009-06
影响因子：
4.3
通讯作者：
N. Saito;J. Hamada;H. Furukawa;A. Tsutsumida;A. Oyama;E. Funayama;A. Saito;T. Tsuji;M. Tada;T. Moriuchi;Yuhei Yamamoto
中科院分区：
文献类型：
--
作者：
N. Saito;J. Hamada;H. Furukawa;A. Tsutsumida;A. Oyama;E. Funayama;A. Saito;T. Tsuji;M. Tada;T. Moriuchi;Yuhei Yamamoto
黑色素瘤极易转移至淋巴结，这是导致预后不良的临床病理因素之一。最近的研究表明淋巴管生成在包括黑色素瘤在内的多种人类肿瘤的淋巴结转移中的重要性。然而，淋巴转移的分子机制仍不明确。我们研究了正常淋巴内皮细胞（LECs）和黑色素瘤细胞之间的相互作用对细胞迁移的影响。LEC培养基（LEC‐CM）对人黑色素瘤细胞系具有趋化和趋化动力学活性。趋化活性在100 kDa以上被分解，并通过热处理灭活。LEC - CM的趋化活性通过抗层粘连蛋白- 1抗体的免疫清除而被消除。免疫沉淀和Western blot分析显示LEC‐CM含有层粘连蛋白421。当整合素α3或α6的功能阻断抗体处理黑色素瘤C8161细胞时，它们对LEC‐CM的趋化反应显着降低。此外，四跨蛋白CD151的敲低削弱了C8161和MeWo细胞对LEC - CM的趋化反应。这些数据表明，LEC分泌的层粘连蛋白421可能通过诱导黑色素瘤细胞趋化促进淋巴转移。
Melanoma has a high tendency to metastasize to lymph nodes, which is one of the clinicopathological factors to indicate poor prognosis. Recent investigations have shown the importance of lymphangiogenesis in lymph node metastasis in a variety of human tumors including melanoma. However, molecular mechanism of lymphatic metastasis is still poorly defined. We examined influence of interactions between normal lymphatic endothelial cells (LECs) and melanoma cells on cell migration. Medium conditioned with LEC (LEC‐CM) contained chemotactic and chemokinetic activities for human melanoma cell lines. The chemotactic activity was fractionated in more than 100 kDa, and inactivated by heat‐treatment. The chemotactic activity of LEC‐CM was abolished by immunodepletion with anti‐laminin‐1 antibody. And immunoprecipitation and Western blot analyses revealed that LEC‐CM contained laminin‐421. When melanoma C8161 cells were treated with function‐blocking antibodies to integrin α3 or α6, their chemotactic responses to LEC‐CM were markedly reduced. Furthermore, the knock‐down of tetraspanin CD151 weakened the chemotactic responses of C8161 and MeWo cells to LEC‐CM. These data suggest that laminin‐421 secreted by LEC possibly facilitates lymphatic metastasis through the induction of chemotaxis of melanoma cells.