Microenvironmental Influences on Metastasis Suppressor Expression and Function during a Metastatic Cell’s Journey

Abstract Metastasis is the process of primary tumor cells breaking away and colonizing distant secondary sites. In order for a tumor cell growing in one microenvironment to travel to, and flourish in, a secondary environment, it must survive a series of events termed the metastatic cascade. Before departing the primary tumor, cells acquire genetic and epigenetic changes that endow them with properties not usually associated with related normal differentiated cells. Those cells also induce a subset of bone marrow-derived stem cells to mobilize and establish pre-metastatic niches [1]. Many tumor cells undergo epithelial-to-mesenchymal transition (EMT), where they transiently acquire morphologic changes, reduced requirements for cell-cell contact and become more invasive [2]. Invasive tumor cells eventually enter the circulatory (hematogenous) or lymphatic systems or travel across body cavities. In transit, tumor cells must resist anoikis, survive sheer forces and evade detection by the immune system. For blood-borne metastases, surviving cells then arrest or adhere to endothelial linings before either proliferating or extravasating. Eventually, tumor cells complete the process by proliferating to form a macroscopic mass [3]. Up to 90 % of all cancer related morbidity and mortality can be attributed to metastasis. Surgery manages to ablate most primary tumors, especially when combined with chemotherapy and radiation. But if cells have dissemi...
Source: Cancer Microenvironment - Category: Cancer & Oncology Source Type: research