Scott G, Cassidy L, Abdel-Malek Z
Department of Dermatology, University of Rochester Medical Center, New York 14642, USA.
Exp Cell Res. 1997 Nov 25;237(1):19-28. doi: 10.1006/excr.1997.3765.
Recent reports show that alpha-MSH (melanocyte-stimulating hormone) is mitogenic and melanogenic for normal human melanocytes, and that this effect is mediated through binding to the melanocortin receptor (MC1R) and activation of cAMP formation. alpha-MSH has also been shown to induce changes in cell shape in melanocytes and melanoma cells, particularly increased dendricity, suggesting a potential role for alpha-MSH in melanocyte-matrix interactions and pigment transfer through reorganization of the melanocyte actin filament cytoskeleton. In this report we show that the potent alpha-MSH analog (Nle4, D-Phe7)-alpha-MSH (NDP-MSH) induces reorganization of the actin stress fiber cytoskeleton in treated human melanocytes and that this reorganization is associated with increased adhesion to fibronectin (FN). Because most melanocyte growth factors act synergistically on melanocyte mitogenesis, we also sought to determine the effect of the melanocyte mitogen endothelin-1 (ET-1) on the melanocyte actin cytoskeleton, melanocyte adhesion, and melanocyte migration. We show that ET-1, which increases melanocyte migration on FN, has opposite effects on melanocyte adhesion to FN compared with NDP-MSH and that endothelin-1-induced actin reorganization is distinct from that observed following NDP-MSH treatment. Finally, we show that focal adhesion kinase (pp125FAK), a nonreceptor tyrosine kinase associated with focal contact formation and cell migration, is phosphorylated on tyrosine residues after treatment of melanocytes with ET-1, but not NDP-MSH. These data indicate that while alpha-MSH and ET-1 act synergistically to modulate melanocyte proliferation, they have opposite effects on melanocyte-matrix interactions.
最近的报告显示，α-促黑素（α-MSH）对正常人黑素细胞具有促有丝分裂和促黑素生成作用，且这种作用是通过与黑素皮质素受体（MC1R）结合并激活环磷酸腺苷（cAMP）形成来介导的。α-MSH还被证明可诱导黑素细胞和黑色素瘤细胞的细胞形态发生变化，尤其是树突增多，这表明α-MSH在黑素细胞-基质相互作用以及通过黑素细胞肌动蛋白丝细胞骨架重组进行色素转移中可能发挥作用。在本报告中，我们表明强效α-MSH类似物（Nle4，D-Phe7）-α-MSH（NDP-MSH）可诱导处理后的人黑素细胞中肌动蛋白应激纤维细胞骨架的重组，且这种重组与对纤连蛋白（FN）的粘附增加有关。由于大多数黑素细胞生长因子对黑素细胞有丝分裂起协同作用，我们还试图确定黑素细胞有丝分裂原内皮素-1（ET-1）对黑素细胞肌动蛋白细胞骨架、黑素细胞粘附和黑素细胞迁移的影响。我们发现，ET-1可增加黑素细胞在FN上的迁移，但与NDP-MSH相比，其对黑素细胞粘附于FN的影响相反，且内皮素-1诱导的肌动蛋白重组与NDP-MSH处理后观察到的不同。最后，我们表明，粘着斑激酶（pp125FAK）是一种与粘着斑形成和细胞迁移相关的非受体酪氨酸激酶，在用ET-1而非NDP-MSH处理黑素细胞后，其酪氨酸残基会发生磷酸化。这些数据表明，虽然α-MSH和ET-1在调节黑素细胞增殖方面起协同作用，但它们对黑素细胞-基质相互作用具有相反的影响。
