Effect of sulfated glycosaminoglycans on tumor invasion and metastasis

Abstract

Metastasis is the most devastating aspect of the tumor, being the main cause of morbidity and mortality in cancer patients. The events that lead to tumor invasion and metastasis depend fundamentally on the initial aquisition of a mesenchymal phenotype by the primary carcinoma, which provides the necessary machinary for invasion, intravasation, vascular transport, extravasation and tumor colonization. These events are orquestrated by different growth factors, proteoglycans and adhesion molecules, acting at the surface of cells. The anticoagulant heparin binds several of these molecules and can regulate the interactions that occur during tumor invasion and metastasis. For example, heparin modulates the binding of FGF-2 to its tyrosine kinase receptor during tumor proliferation, and the binding of growth factors involved in epithelial to mesenchymal transition during tumor invasion. It also binds P-selectin on activated platelets, preventing tumor cell-platelet interaction during hematogeneous metastasis. In this review, we discuss the role of sulfated glycosaminoglycans during tumor invasion and metastasis, and the possible therapeutic use of heparin analogs on cancer treatment.