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      How and when do tumor cells metastasize?

      Critical reviews in oncogenesis
      Animals, Genes, Tumor Suppressor, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, genetics, pathology, Neoplasms, Experimental, Time Factors

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          Abstract

          Tumor cells metastasize when they have successfully passed a number of invasion steps. We hypothesize that each step is a microecosystem, the basic elements of which are neoplastic cells, host cells, and extracellular matrix (ECM). We review here molecular pathways with a regulatory function in these microecosystems: homotypic cell-cell adhesion molecules counteracting invasion; complexes of lytic (pro-)enzymes, their receptors and inhibitors regulating focalized breakdown of the ECM; matrix components, their cellular receptors and motility factors governing cell migration; heterotypic cell-cell adhesion molecules initiating extravasation, encompassing in the vasculature the sequence: cell arrest, 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 invasion events leading to metastasis.

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