E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors
E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors
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DOI：
10.1016/s0002-9440(10)65023-7
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发表时间：
2000-05-01
影响因子：
6
通讯作者：
Herlyn, M
中科院分区：
文献类型：
--
作者：
Hsu, MY;Meier, FE;Herlyn, M
在人类表皮中，功能性共生需要角质形成细胞和黑素细胞之间的稳态平衡。来自共培养研究的令人信服的证据表明，未分化的基底型角质形成细胞对正常黑素细胞表型进行复杂的、多层次的调节。角质形成细胞控制细胞的生长和树突，以及正常黑素细胞的黑色素瘤相关细胞表面分子的表达。相反，黑色素瘤细胞对角质形成细胞介导的调节是难治的。角质形成细胞调控优势的丧失与黑色素瘤细胞中E-钙粘蛋白表达的下调一致。为了研究E-钙粘蛋白在黑色素角化细胞相互作用中的潜在作用，我们使用腺病毒载体用全长E-钙粘蛋白cDNA转导E-钙粘蛋白阴性黑色素瘤细胞。我们的研究结果表明，功能性E-钙粘蛋白在黑色素瘤细胞中的表达导致细胞粘附到角质形成细胞，使其对角质形成细胞介导的控制敏感。在皮肤重建模型中，异位E-cadherin表达通过下调侵袭相关的粘附受体Me 1CAM/MUC 18和β 3整合素亚基以及诱导细胞凋亡来抑制黑色素瘤细胞侵入真皮。因此，破坏E-钙粘蛋白介导的，正常的调节控制从角质形成细胞可能代表的机制之一，占黑素细胞转化。
In human epidermis, functional symbiosis requires homeostatic balance between keratinocytes and melanocytes, Compelling evidence from co-culture studies demonstrated a sophisticated, multileveled regulation of normal melanocytic phenotype orchestrated by undifferentiated, basal-type keratinocytes. Keratinocytes control cell growth and dendricity, as well as expression of melanoma-associated cell surface molecules of normal melanocytes, In contrast, melanoma cells are refractory to the keratinocyte-mediated regulation. The loss of regulatory dominance by keratinocytes occurs in concert with down-regulation of E-cadherin expression in melanoma cells. To investigate the potential role of E-cadherin in melanomakeratinocyte interaction, we transduced E-cadherin-negative melanoma cells with full-length E-cadherin cDNA using an adenoviral vector. Our results show that functional E-cadherin expression in melanoma cells leads to cell adhesion to keratinocytes rendering them susceptible for keratinocyte-mediated control. In a skin reconstruction model, ectopic E-cadherin expression inhibits invasion of melanoma cells into dermis by down-regulating invasion-related adhesion receptors, Me1CAM/MUC18 and beta 3 integrin subunit, and by induction of apoptosis. Thus, disruption of the E-cadherin-mediated, normal regulatory control from keratinocytes may represent one of the mechanisms accounting for melanocyte transformation.