The cells are separated by a physical barrier, called basal lamina, which underlies layers of epithelial cells as well as surrounds endothelial cells. The cancer cells become matastatic and their basement membrane is being distorted and they escape from the original tissue, invade adjoining tissues and finally through circulation spreads throughout the body. Again they form cancerous secondary tumor at their new invading regions.
Tumor cells produce an elevated level of cell surface receptor specific protein, carbohydrates composing basal lamina eg. collagens, proteoglycans and glycosaminoglycans. They also secrete a protease called plasminogen activator, which cleaves a peptide bond in the serum protein plasminogen; converting it into plasmin. Small amount of plasminogen activator causes formation of large amount plasmin by chain reaction. Plasmin is a protease. It digests and penetrates basal lamina and promotes metastasis by degenerating the basal lamina of the cell.
During metastasis, tumor cells may enter the blood stream directly by crossing the wall of the blood vessel or more commonly by crossing the wall of the lymphatic vessels, that ultimately discharges its contents, i.e., lymph into the blood stream. Tumor cells that have entered into lymphatic vessels often become trapped in lymph nodes along the way and causes lymph node metastasis. They again through the circulation may be trapped in lung, kidney and other organs and start propagation at their new sites.
For cell-cell adhesion, E-cadherin proteins are essential, which are embedded in two adjacent plasma membranes to bind the epithelial cells together. In some stomach and of the breast, the E-cadherin gene has been identified as a tumor suppression gene. When tumor cells lacking this adhesion molecule, are placed in culture, a functional E-cadherin gene is put back into them, then the invasive characteristics of these cells are lost. So, loss of E-cadherin gene may favour cancer particularly to aquirmetastatic properly.
During metastsis three steps are involved. Firstly, the escape from the original tissue and entry into the blood stream or lymphatic channel. Secondly, the metastatic cells travel through the circulation. These cells survive in this path, arrest in the capillaries or other small vessels and then exit into the remote tissue organs. The third step is crucial for these metastatic cells before colonization at the remote site. Most of the losses occur after this. Some cells die immediately, some cells enter into the foreign tissue but fail to grow, still others divide a few times and then stop. Here the metastasis competent cells outperform their nonmetastatic relatives. Therefore, it may be suggested that the ability to grow in the foreign tissue is a key property that cells must acquire to become metastatic.
A number of genes have been shown to be active in the malignant cells. Over-expression of Rho-C gene has been observed in the metastatic cells. Rho-C is a member of a family of genes known to regulate cell mortality.
The molecular mechanism of metastasis is still unknown.