Versican: Role in Cancer Tumorigenesis

Abstract

Versican is an extracellular matrix proteoglycan that is expressed in a wide variety of cancers. Several cellular sources for versican have been identified in a multitude of cancers including tumor cells, stromal cells, myeloid cells, and lymphoid cells. Versican plays a role in five of the six hallmarks of cancer including proliferative signaling, evasion of growth suppressor signaling, promotion of tissue invasion and metastasis, angiogenesis, and resistance to cell death. Versican also interacts with growth factors and cytokines to modify their activity and involvement in the cancer response. The synthesis and accumulation of versican is regulated by similar pathways that regulate cancer progression, such as the canonical Wnt/β-catenin pathway and receptor tyrosine kinases. The expression and accumulation of versican are associated with poor prognosis, disease progression, metastasis, and chemoresistance. A detailed analysis of the role of versican in the disease course of leiomyosarcoma is provided here as an example of the importance of this extracellular matrix component in cancer pathogenesis. Collectively, our results and those from other groups suggest that versican could serve as a point of control in the management and treatment of many cancers.