Department of Molecular Oncology, Cancer Institute WIA, Chennai, Tamil Nadu, India.
Deaprtment of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India.
Gene. 2022 Mar 20;815:146137. doi: 10.1016/j.gene.2021.146137. Epub 2022 Jan 7.
The extracellular matrix (ECM) is composed of a mesh of proteins, proteoglycans, growth factors, and other secretory components. It constitutes the tumor microenvironment along with the endothelial cells, cancer-associated fibroblasts, adipocytes, and immune cells. The proteins of ECM can be functionally classified as adhesive proteins and matricellular proteins (MCP). In the tumor milieu, the ECM plays a major role in tumorigenesis and therapeutic resistance. The current review encompasses thrombospondins, osteonectin, osteopontin, tenascin C, periostin, the CCN family, laminin, biglycan, decorin, mimecan, and galectins. The matrix metalloproteinases (MMPs) are also discussed as they are an integral part of the ECM with versatile functions in the tumor stroma. In this review, the role of these proteins in tumor initiation, growth, invasion and metastasis have been highlighted, with emphasis on their contribution to tumor therapeutic resistance. Further, their potential as biomarkers and therapeutic targets based on existing evidence are discussed. Owing to the recent advancements in protein targeting, the possibility of agents to modulate MCPs in cancer as therapeutic options are discussed.
细胞外基质（ECM）由蛋白质、蛋白聚糖、生长因子和其他分泌成分组成的网状物构成。它与内皮细胞、癌相关成纤维细胞、脂肪细胞和免疫细胞一起构成肿瘤微环境。ECM 的蛋白质可以分为黏附蛋白和基质细胞衍生蛋白（MCP）。在肿瘤微环境中，ECM 在肿瘤发生和治疗抵抗中起着重要作用。目前的综述包括血栓素、骨桥蛋白、骨黏连蛋白、腱糖蛋白 C、成纤维细胞附着蛋白、CCN 家族、层粘连蛋白、核心蛋白聚糖、聚集蛋白聚糖、微小染色体维持蛋白和半乳糖凝集素。还讨论了基质金属蛋白酶（MMPs），因为它们是 ECM 的一个组成部分，在肿瘤基质中具有多种功能。在这篇综述中，强调了这些蛋白质在肿瘤起始、生长、侵袭和转移中的作用，并重点讨论了它们对肿瘤治疗抵抗的贡献。此外，还根据现有证据讨论了它们作为生物标志物和治疗靶点的潜力。由于蛋白质靶向的最新进展，讨论了作为治疗选择的针对 MCP 的药物的可能性。
