Cancers spread by both local invasion and by metastasis in vessels of the blood or lymphatic systems. Infiltration into surrounding tissues is associated with loss of cell-cell cohesion. Cohesion is mediated by active homotypic cell adhesion molecules (CAMs). The cadherin molecules are transmembrane glycoproteins able to mediate cellular attachment. Epithelial cadherin (E-cadherin) is expressed by many carcinomas, e.g. gastric carcinoma, and loss of E-cadherin expression is associated with an increase in invasion of the tumour.

Invasion is partly determined by the balance of activators to inhibitors of proteolysis. Secretion of proteolytic enzymes, including the matrix metalloproteinases (particularly the collagenases), occurs from adjacent fibroblasts owing to failure of production of tissue inhibitors. The balance between the expression and activity of the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in tumour growth, invasion, metastasis and angiogenesis. Some TIMPs may regulate cell proliferation and survival of cancer cells independently of MMP activity.

Dissemination of tumour cells occurs when they enter the vascular and lymphatic vessels. Here they must survive host-defence mechanisms so as to spread throughout the body. The disseminated cancer cells lodge in distant sites, partly by chance, but also because of specific interactions between receptors/ligands found on endothelial cells and on tumour cells. This may account for the specific pattern of metastases with certain tumours; for example, breast tumours frequently metastasize to long bones (see below).

The attachment of tumour cells to the endothelial cells is partly through adhesion molecules. Integrins are transmembrane heterodimeric glycoproteins formed by non-covalent association of α and β chains. These molecules are normally responsible for cell-substrate adhesion. Patterns of integrin expression in tumours are complex but, nevertheless, certain tumours demonstrate upregulation of specific integrins, such as the alpha v family, during tumour progression, and this may allow migration of tumour cells through the extracellular matrix substrate and invasion through the basement membrane and formation of a metastatic deposit. Integrins also act as receptors for signals regulating gene expression and apoptosis.

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1. [...] cadherin Health Nova: Your Ultimate Medical Portal Invasion and …The cadherin molecules are transmembrane glycoproteins able to mediate cellular … Epithelial [...]

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