Interplay of integrins and selectins in metastasis

Metastasis is a hallmark of malignancy and poses a formidable challenge for oncologists. This complex process begins when the primary malignant cells start to proliferate unlimitedly. Once the tumor reaches a certain size, cancer cells detach from the primary tumor mass and the basal lamina to which they are anchored, eventually invading nearby blood vessels. Within the bloodstream, these tumor cells have to survive and attach to the endothelium at distant sites. Cell-to-cell and cell-to-matrix interactions play an important role during these stages, in which integrins-a family of cell adhesion molecules (CAMs)-stand out as functionally centrally involved. Their expression on the tumor cell surface needs to be dynamically regulated throughout the process of metastasis. During the attachment phase to the endothelium, another group of CAMs, such as E-/P-selectins-primarily expressed on endothelial cells-may also play a critical role in certain malignancies. Additionally, the interplay between integrins and selectins may influence the tumor microenvironment. This review focuses on the role of integrins and their interplay with selectins in metastasis, emphasizing findings from in vivo studies.