Metastatic colonization: settlement, adaptation and propagation of tumor cells in a foreign tissue environment

Disseminated tumor cells must negotiate multiple situations that challenge their viability and/or proliferative capacity before they can successfully colonize distant organ sites. Thus, the shear stress caused by the blood flow may physically damage tumor cells during their translocation from primary tumors to distant organs via the circulation. In addition, the tissue microenvironment of distant organs is generally unfamiliar to tumor cells, limiting their proliferation within the parenchyma of these organs. Each of these situations involves various types of interactions between tumor cells and host components, which either support or inhibit the establishment and subsequent progression of metastases. The initial formation of micrometastases, as well as their subsequent growth--often termed colonization--therefore require complex adaptations by tumor cells to various host components, most of which are never encountered by these cells during their growth within primary tumor sites. These difficulties explain why the colonization of distant organs by disseminated tumor cells is an extraordinarily demanding task and thus inefficient, and suggests a number of potential targets that might be used in the future to interfere therapeutically with this process. Studying the details of tumor-host interactions at each of the steps leading up to successful metastatic colonization may therefore pave the way for designing therapeutic strategies to counteract the metastatic spread of malignant tumors.