Proteoglycans and cell adhesion

Abstract

In this review, evidence that proteoglycans are involved in cell adhesion and related behavior is considered, together with their putative role(s) during tumorigenesis. Proteoglycans are large, carboxylated and/or sulfated structures that interact with specific binding sites on cell surfaces. Their distribution and synthesis in tissues alter with the onset of tumorigenesis so that hyaluronic acid is generally increased and heparan sulfate decreased in the developing tumor and surrounding tissue. However, the precise role of proteoglycans during the tumorigenic process is far from clarified. Data suggest any putative roles will be related to the adhesive properties that these molecules confer to cells. Hyaluronic acid and chondroitin sulfate appear to be weakly adhesive molecules that may promote 'transformed' characteristics when they occur on cells in large amounts. These characteristics include reduced cell spreading, increased cell motility, as well as reduced contact inhibition. Consistent with such properties, neither hyaluronic acid nor chondroitin sulfate are localized in specialized adhesion sites such as focal or close contacts. In contrast, heparan sulfate is associated with increased cell-substratum adhesion and is involved in the spreading of cells onto fibronectin and other substrata. Its presence is generally associated with reduced motility and with a well-spread morphology. Unlike hyaluronate and chondroitin sulfate, heparan sulfate is found in specialized contacts. These adhesive properties of proteoglycans predict an instructive role in tumor development, and recent experiments have defined an involvement of these molecules in metastatic arrest. Additional studies utilizing invasive and metastatic tumor variants including tumor cells that employ different mechanisms to invade are required to clarify the role of proteoglycans in tumor progression.

Carbohydrate structure in tumor immunity

“…For more information on GAGs and neoplasia and for references see the referenced reviews (182)(183)(184)(185)(186). Tumor-associated alterations in content or structure have been reported for all of these GAGs.…”

Increased content of chondroitin sulfate proteoglycan in human colorectal carcinoma metastases compared with the primary tumor as determined by an anti‐chondroitin‐sulfate monoclonal antibody

“…Proteoglycans are major constituents of the connective tissue stroma of most organs and are involved in tissue organization and other biological processes, such as cell proliferation and migration [14][15][16]. Altered levels of proteoglycan production and release and changes in the structure of glycosaminoglycan chains have been reported in a variety of transformed cells and tumor tissues [17,18]. Increased production of chondroitin sulfate proteoglycan (CSPG) has been reported in transformed fibroblasts [ 191 and hepatocytes [20] as well as in more tumorigenic melanoma and mammary carcinoma [21,22].…”

Scaffolds of Hyaluronic Acid–Poly(Ethyl Acrylate) Interpenetrating Networks: Characterization and In Vitro Studies

“…At days 5 and 10, cell metabolic activity in the HA and IPN scaffolds was significantly higher than in PEA, with IPN scaffolds showing the highest index of metabolic activity. This may be unexpected, since PEA is more cell‐adherent than HA . A number of reasons may be responsible for this finding.…”