Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes 1524, Prédio I, sala 428, 05508-000, São Paulo, SP, Brazil.
Int J Mol Sci. 2018 Oct 24;19(11):3300. doi: 10.3390/ijms19113300.
The extracellular matrix (ECM) is a crucial component of the tumor microenvironment involved in numerous cellular processes that contribute to cancer progression. It is acknowledged that tumor⁻stromal cell communication is driven by a complex and dynamic network of cytokines, growth factors and proteases. Thus, the ECM works as a reservoir for bioactive molecules that modulate tumor cell behavior. The hepatocyte growth factor (HGF) produced by tumor and stromal cells acts as a multifunctional cytokine and activates the c-MET receptor, which is expressed in different tumor cell types. The HGF/c-MET signaling pathway is associated with several cellular processes, such as proliferation, survival, motility, angiogenesis, invasion and metastasis. Moreover, c-MET activation can be promoted by several ECM components, including proteoglycans and glycoproteins that act as bridging molecules and/or signal co-receptors. In contrast, c-MET activation can be inhibited by proteoglycans, matricellular proteins and/or proteases that bind and sequester HGF away from the cell surface. Therefore, understanding the effects of ECM components on HGF and c-MET may provide opportunities for novel therapeutic strategies. Here, we give a short overview of how certain ECM components regulate the distribution and activation of HGF and c-MET.
细胞外基质（ECM）是肿瘤微环境的重要组成部分，参与了许多细胞过程，这些过程有助于癌症的进展。人们已经认识到，肿瘤⁻基质细胞通讯是由细胞因子、生长因子和蛋白酶的复杂和动态网络驱动的。因此，ECM 作为生物活性分子的储存库，调节肿瘤细胞的行为。肿瘤和基质细胞产生的肝细胞生长因子（HGF）作为一种多功能细胞因子，激活在不同肿瘤细胞类型中表达的 c-MET 受体。HGF/c-MET 信号通路与多种细胞过程有关，如增殖、存活、迁移、血管生成、侵袭和转移。此外，c-MET 的激活可以被几种 ECM 成分促进，包括作为桥连分子和/或信号共受体的糖蛋白和蛋白聚糖。相反，c-MET 的激活可以被与 HGF 结合并将其从细胞表面隔离的蛋白聚糖、基质细胞蛋白和/或蛋白酶抑制。因此，了解 ECM 成分对 HGF 和 c-MET 的影响可能为新的治疗策略提供机会。在这里，我们简要概述了某些 ECM 成分如何调节 HGF 和 c-MET 的分布和激活。
