HOW AND WHEN DO TUMOR-CELLS METASTASIZE

Tumor cells metastasize when they have successfully passed a number of invasion steps. We hypothesize that each step is a microecosystem, th e basic elements of which are neoplastic cells, host cells, and extrac ellular matrix (ECM). We review here molecular pathways with a regulat ory function in these microecosystems: homotypic cell-cell adhesion mo lecules counteracting invasion; complexes of lytic (pro-)enzymes, thei r receptors and inhibitors regulating focalized breakdown of the ECM; matrix components, their cellular receptors and motility factors gover ning cell migration; heterotypic cell-cell adhesion molecules initiati ng extravasation, encompassing in the vasculature the sequence: cell a rrest, ECM lysis, cell migration; factors allowing survival and growth at ectopic sites. We conclude that delicate molecular balances within microecosystems are, responsible for the temporary and repeated invas ion events leading to metastasis.