Intercellular adhesion: Mechanisms for growth and metastasis of epithelial cancers

Cell-cell adhesion molecules (CAMs) comprise a broad class of linker proteins that are crucial for the development of multicellular organisms, and for the continued maintenance of organ and tissue structure. Because of its pivotal function in tissue homeostasis, the deregulation of intercellular adhesion is linked to the onset of most solid tumors. The breakdown of homeostatic cell adhesions in highly ordered epithelial sheets is directly implicated in carcinogenesis, while continued changes in the adhesion profile of the primary tumor mass facilitate growth and expansion into adjacent tissue. Intercellular adhesion molecules are also involved in each subsequent phase of metastasis, including transendothelial migration, transit through the bloodstream or lymphatics, and renewed proliferation in secondary sites. This review addresses various roles of cadherin- and selectin-mediated intercellular adhesion in tumor initiation and malignant transformation, and discusses the mechanisms for the arrest and adhesion of circulating tumor cells to the vessel endothelium. Considering the contributions of these CAMs to cancer progression in the context of a systematic biological framework may prove valuable in identifying new ways to diagnose and treat cancer.