Cell Surface Chondroitin Sulfate Proteoglycans in Tumor Cell Adhesion, Motility and Invasion

Tumor cell invasion and metastasis is highly dependent on dynamic changes in the adhesion and migration of transformed and malignant cells. As with normal cell adhesion, the adhesion of tumor cells influences their cytoskeletal organization, activation of signal transduction pathways within the cell, and nuclear events leading to changes in mRNA transcription and protein synthesis. Furthermore, as tumor cells invade the circulation, they adhere to activated endothelial cells at sites within the vasculature during arrest and extravasation. Studies in the area of tumor cell adhesion and migration have demonstrated that the recognition of extracellular matrix ligands, or adhesion promoting ligands expressed on neighboring cells (i.e. counter-receptors), involves complex molecular recognition mechanisms. The complexity arises, in part, from the multiple recognition sites that are present within adhesion promoting ligands. Some of these structures within ECM components act by binding integrins, whereas others bind additional receptors such as cell surface proteoglycans. In this sense, adhesion promoting ligands may be considered as informational arrays, that function to modulate cell phenotype by engaging specific combinations of adhesion receptors on the cell surface. Understanding the mechanism(s) by which these receptor 'cluster' modify cell adhesion, motility and growth may lead to novel therapeutic strategies to control tumor cell invasion and metastasis formation. This review will highlight the role that cell surface chondroitin sulfate proteoglycans may play in modulating tumor cell adhesion, migration and invasion, with an emphasis on the relationship between cell surface chondroitin sulfate proteoglycans and integrins.