Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada.
Département de Médecine, Université de Montréal, Montréal, Québec, Canada.
Cancer Res. 2020 Jul 1;80(13):2705-2717. doi: 10.1158/0008-5472.CAN-18-2098. Epub 2020 Mar 19.
The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCP) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets.
细胞外基质(ECM)对于调节细胞行为是不可或缺的。ECM 信号的动态变化在生长和发育过程中受到严格控制。在组织重塑过程中,细胞基质蛋白(MCP)被分泌到 ECM 中。这些因子不具有经典的结构作用,而是调节基质蛋白和细胞-基质相互作用,以影响正常细胞功能。在肿瘤微环境中,越来越明显的是,异常表达的 MCP 可以通过与各种与一系列下游信号相关联的细胞成分相互作用,来支持致癌作用的多个特征。此外,MCP 还可以重新组织 ECM 的生物力学特性,以适应转移和肿瘤定植。这一认识正在激发对 MCP 作为癌症中可靠和可及的生物标志物以及有效和选择性治疗靶点的新研究。