The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities

摘要

Metastasis, the process by which cancer cells escape primary tumor site and colonize distant organs, is responsible for most cancer-related deaths. The tumor microenvironment (TME), comprises different cell types, including immune cells and cancer-associated fibroblasts, as well as structural elements, such as collagen and hyaluronan that constitute the extracellular matrix (ECM). Intratumoral interactions between the cellular and structural components of the TME regulate the aggressiveness, and dissemination of malignant cells and promote immune evasion. At the secondary site, the TME also facilitates escape from dormancy to enhance metastatic tumor outgrowth. Moreover, the ECM applies mechanical forces on tumors that contribute to hypoxia and cancer cell invasiveness whereas also hinders drug delivery and efficacy in both primary and metastatic sites. In this review, we summarize the latest developments regarding the role of the TME in cancer progression and discuss ongoing efforts to remodel the TME to stop metastasis in its tracks.