Versican is an extracellular matrix (ECM)
proteoglycan that interacts with cells by binding to non-
integrin and
integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that
versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory
cytokines.
Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in
inflammation. Inflammatory agonists, such as
double-stranded RNA mimetics (e.g.,
poly I:C), stimulate stromal cells, smooth muscle cells and fibroblasts, to produce fibrillar ECMs enriched in
versican and
hyaluronan (HA) that interact with leukocytes promoting their adhesion. Interference with the incorporation of
versican into this ECM blocks monocyte adhesion and dampens the inflammatory response.
Tumor cells also express elevated levels of
versican which interact with myeloid cells to promote an inflammatory response, through stimulating
cytokine release, and
metastasis. In addition, myeloid cells, such as macrophages in
tumors, synthesize
versican which affects
tumor cell phenotypes,
inflammation, and subsequent
metastasis.
Versican, by binding to
hyaluronan, influences T lymphocyte phenotypes and in part controls the ability of these cells to synthesize and secrete
cytokines that influence the immune response. Collectively, these studies indicate that
versican as an ECM molecule plays a central role in
inflammation and as a result it is emerging as a potential target promising wide therapeutic benefits.