The metastatic process

All the malignant tumors possess the same characteristic to form distant secondary tumors or metastasis. The acquisition of the metastatic potential takes place in random accumulation of different genetic and cellular changes. Their combination allows one or several tumor cells to achieve the whole metastatic process. The metastatic process involves numerous interactions between the tumor cells and the host cells of the tumor cells and the extracellular matrix. The attachment of the metastatic cells to the extracellular matrix specific glycoproteins involves cell surface receptors as integrins, sialyled residues or CD44. On the other hand, other adhesive molecules (Cadherins) display inhibitory action on the metastatic process. The enzymatic lysis is carried out by glycolytic enzymes and proteases: metalloproteases (inhibitors TIMP1 et TIMP2), serine proteases (tPA, uPA-inhibitors: PAI1 and PAI2). Cathepsin D or Heparanases. Several enzymes may be necessary for the degradation of the basal membrane. The crossing of both basal membrane and stroma can be made on account of the cell motility. Some factors can modify this property as AMF (Autocrin Motility Factor) or ATX (Autotoxin) but the molecular mechanisms involved in the migration are not yet completely understood. The last stage is relative to the cells proliferation in the site organ; it depends on autocrine (CSF1, IL2, Bombesine...) or some paracrine growth factors. However, the formation of metastasis is possible only in the site organ attaching the cells.