Cellular and molecular mechanisms of tumor invasion.

This review summarizes data on cellular and molecular mechanisms underlying phenotypical characteristics of tumor cells that determine their ability for invasion. These mechanisms include dysregulation of adhesive interactions of tumor cells with each other and with extracellular matrix, protease production, locomotion reactions of tumor cells, and induction of angiogenesis in tumor. Data on structure and functions of transmembrane adhesion molecules and their ligands, molecular composition of adhesion structures (intercellular and focal contacts), and role of adhesion molecules as transducers of intracellular signals are considered. Alterations of expression of adhesion molecules and cytoplasmic proteins in adhesion structures and hyperphosphorylation of these molecules by oncogene products are described as a precondition of invasion activity of tumor cells. The contact interaction between circulating tumor cells and vascular endothelium is considered as the important stage of the metastatic process. Secretion of proteases by tumor cells and regulation of their activity by specific stromal inhibitors are described. Function of motogens in the acquisition by a tumor cell of locomotor phenotype facilitating invasion and impairments of topographic reactions of cells playing an important role in the invasion are considered. Attention is given to mechanisms of neoangiogenesis in the tumor providing additional ways for dissemination of tumor cells.