Biologic of metastases

Abstract

Death from cancer is usually due to metastasis. Fortunately, most cells that escape from a primary tumor fail to form metastases. Recent advances in the understanding of the metastatic process suggest that it is a five-step process including angiogenesis, adhesion, proteolysis, migration and proliferation. Angiogenesis is the fundamental process required for a number of physiological and pathological events and is considered to be a key step in tumor growth, invasion, and metastasis. Angiogenesis is necessary at the beginning of the metastatic cascade, because newly formed blood vessels can provide nutrition for the cancer cells. Several angiogenetic factors have been found to be produced by tumor and normal tissues. Many thousands of cells may enter venous drainage system of the tumor each day and travel to other regions of body. Tumour cell adhesion may be required for both entering the vascular conduits and adhering to the secondary sites. Adhesion molecules attaching to cell surface receptors and their ECM counter-ligands may function through two mechanisms of action. The first mechanism may involve interactions such as those between the cadherin and integrin cell surface receptors, resulting in the anchoring of tumour cells and inhibition of their movement. The second mechanism may be represented by CD44 which facilitates tumoral behaivour. Cadherin family is one of the most important adhesion molecules for maintaining multicellular structures. Down-regulation of E-cadherin gene expresion might cause cancer cell detachment and thus promote cell metastasis. Cancer cell migration is regulated by some factors, such as, extracellular matrix components, growth factors, and the autocrine motility factors. Tumour cells usually migrate within venous and lymphatic circulation until they lodge in the next capillary bed or lymph node by adhering to the vessells inner lining. There may be a suitable "soil" for cancer cells to survive and grow in other organs. This "soil" may include hormones, growth factors and/or adhesion molecules. Actually, most of the cancer cells die during travelling. Only those cancer cells that begin to proliferate will initiate a new colony. Therefore, only very few tumor cells that can leave the primary tumor survive to start new tumor colonies.