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

Cancers

Triantafyllos Stylianopoulos¹  Myrofora Panagi¹  Panagiotis Papageorgis²  ChristianaM. Neophytou² 

[1] Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, 2109 Nicosia, Cyprus;European University Research Center, 2404 Nicosia, Cyprus;

关键词: tumor microenvironment;    immune system;    metastasis;    drug delivery;    cancer therapy;   

DOI  :  10.3390/cancers13092053

来源: DOAJ

【 摘 要 】

The tumor microenvironment (TME) regulates essential tumor survival and promotion functions. Interactions between the cellular and structural components of the TME allow cancer cells to become invasive and disseminate from the primary site to distant locations, through a complex and multistep metastatic cascade. Tumor-associated M2-type macrophages have growth-promoting and immunosuppressive functions; mesenchymal cells mass produce exosomes that increase the migratory ability of cancer cells; cancer associated fibroblasts (CAFs) reorganize the surrounding matrix creating migration-guiding tracks for cancer cells. In addition, the tumor extracellular matrix (ECM) exerts determinant roles in disease progression and cancer cell migration and regulates therapeutic responses. The hypoxic conditions generated at the primary tumor force cancer cells to genetically and/or epigenetically adapt in order to survive and metastasize. In the circulation, cancer cells encounter platelets, immune cells, and cytokines in the blood microenvironment that facilitate their survival and transit. This review discusses the roles of different cellular and structural tumor components in regulating the metastatic process, targeting approaches using small molecule inhibitors, nanoparticles, manipulated exosomes, and miRNAs to inhibit tumor invasion as well as current and future strategies to remodel the TME and enhance treatment efficacy to block the detrimental process of metastasis.

【 授权许可】

Unknown