Cellular interactions in the vascular niche: implications in the regulation of tumor dormancy

Angiogenesis plays an established role in the promotion of growth of dormant micrometastasis, because blood vessels deliver oxygen and nutrients to the tumor microenvironment. In addition to this feeding function, however, there is accumulating evidence suggesting that endothelial cells-and perhaps other cellular components of the microenvironment--could communicate both positive and negative signals to tumor cells. This cross-talk between heterogeneous cell types could turn out to be important in the regulation of cancer cell behavior. Normal cells recruited during the angiogenic process, or attracted to future sites of metastasis by soluble products released by cancer cells, have been shown to create a niche favorable to tumor cell proliferation and survival. In addition, following an exogenous angiogenic spike, as may occur during inflammation, the same mechanisms could lead to re-activation of poorly angiogenic tumor cells seeded into tissues. In this review, we discuss the possible implications of this hypothesis for our understanding of the phenomenon of tumor dormancy.