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.