Makowiecka A, Simiczyjew A, Nowak D, Mazur A J
University of Wrocław, Department of Cell Pathology.
Eur J Histochem. 2016 Dec 9;60(4):2728. doi: 10.4081/ejh.2016.2728.
The understanding of melanoma malignancy mechanisms is essential for patient survival, because melanoma is responsible for ca. 75% of deaths related to skin cancers. Enhanced formation of invadopodia and extracellular matrix (ECM) degradation are two important drivers of cell invasion, and actin dynamics facilitate protrusive activity by providing a driving force to push through the ECM. We focused on the influence of epidermal growth factor (EGF), hepatocyte growth factor (HGF) and transforming growth factor β (TGFβ) on melanoma cell invasiveness, since they are observed in the melanoma microenvironment. All three factors stimulated invasion of A375 and WM1341D cells derived from primary tumor sites. In contrast, only EGF and HGF stimulated invasion of WM9 and Hs294T cells isolated from lymph node metastases. Enhanced formation of invadopodia and ECM degradation underlie the increased amount of invasive cells after stimulation with the tested agents. Generally, a rise in invasive potential was accompanied by a decrease in actin polymerization state (F:G ratio). The F:G ratio remained unchanged or was even increased in metastatic cell lines treated with TGFβ. Our findings indicate that the effects of stimulation with EGF, HGF and TGFβ on melanoma cell invasiveness could depend on melanoma cell progression stage.
了解黑色素瘤的恶性机制对患者的生存至关重要，因为黑色素瘤导致了约75%的皮肤癌相关死亡。侵袭性伪足的形成增强和细胞外基质（ECM）降解是细胞侵袭的两个重要驱动因素，而肌动蛋白动力学通过提供推动力以穿过ECM来促进突出活动。我们关注表皮生长因子（EGF）、肝细胞生长因子（HGF）和转化生长因子β（TGFβ）对黑色素瘤细胞侵袭性的影响，因为它们在黑色素瘤微环境中被观察到。这三种因子均刺激了源自原发性肿瘤部位的A375和WM1341D细胞的侵袭。相比之下，只有EGF和HGF刺激了从淋巴结转移灶分离出的WM9和Hs294T细胞的侵袭。侵袭性伪足形成增强和ECM降解是受试药物刺激后侵袭性细胞数量增加的基础。一般来说，侵袭潜能的增加伴随着肌动蛋白聚合状态（F:G比值）的降低。在用TGFβ处理的转移性细胞系中，F:G比值保持不变甚至增加。我们的研究结果表明，EGF、HGF和TGFβ刺激对黑色素瘤细胞侵袭性的影响可能取决于黑色素瘤细胞的进展阶段。
