Keratinocyte-derived Laminin-332 Promotes Adhesion and Migration in Melanocytes and Melanoma
Keratinocyte-derived Laminin-332 Promotes Adhesion and Migration in Melanocytes and Melanoma
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DOI：
10.1074/jbc.m110.166751
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发表时间：
2011-04-15
影响因子：
4.8
通讯作者：
Oh, Eok-Soo
中科院分区：
文献类型：
--
作者：
Chung, Heesung;Suh, Eun-Kyung;Oh, Eok-Soo
黑素细胞是高度运动的细胞，在皮肤的基本生理过程中起着不可或缺的作用，如伤口愈合和皮肤色素沉着。据推测，周围的角质形成细胞有助于黑素细胞的迁移，但潜在的机制迄今仍相当模糊。在这项研究中，我们着手分析角质细胞成分对黑色素细胞和黑色素瘤细胞迁移相关过程的具体潜在贡献。我们的研究表明，HaCaT角质细胞细胞外基质（ECM）比自身衍生的A375 ECM更能支持A375人黑色素瘤细胞的附着、扩散和迁移。此外，HaCaT ECM引起整合素α 6表达增加，粘附介导的局灶粘附激酶磷酸化和局灶粘附形成。在人类黑素细胞中也证实了类似的效果。此外，我们发现角质形成细胞衍生的可溶性因子似乎对这些过程没有显著贡献。促进黑色素瘤迁移的特定外部因素归因于角质形成细胞衍生的层粘连蛋白332，而其他ECM成分，如层粘连蛋白111和纤维连接蛋白功能似乎没有显著贡献。综上所述，这些研究提示外源性层粘连蛋白332分别促进了黑素细胞和黑素瘤的高迁移性和可能的侵袭性固有特征。
Melanocytes are highly motile cells that play an integral role in basic skin physiological processes such as wound healing and proper skin pigmentation. It has been postulated that surrounding keratinocytes contribute to melanocyte migration, but underlying mechanisms remain rather vague so far. In this study, we set out to analyze the specific potential contribution of keratinocyte components to melanocytes and melanoma cell migration-related processes. Our studies revealed that A375 human melanoma cell attachment, spreading, and migration are interestingly better supported by HaCaT keratinocyte extracellular matrix (ECM) than by self-derived A375 ECM. Moreover, HaCaT ECM caused increased integrin alpha 6 expression, adhesion-mediated focal adhesion kinase phosphorylation, and focal adhesion formations. Similar effects were confirmed in human melanocytes. Furthermore, we found that keratinocyte-derived soluble factors did not appear to significantly contribute to these processes. Specific extrinsic factors that promoted melanoma migration were attributed to keratinocyte-derived laminin-332, whereas alternative ECM component such as laminin-111 and fibronectin functions appeared to have insignificant contributions. Taken together, these studies implicate extrinsic laminin-332 in promoting the high mobility property and perhaps invasiveness inherently characteristic of, and that are the menace of, melanocytes and melanomas, respectively.