Versican in the Tumor Microenvironment.

Abstract

Versican is an extracellular matrix proteoglycan with nonredundant roles in diverse biological and cellular processes, ranging from embryonic development to adult inflammation and cancer. Versican is essential for cardiovascular morphogenesis, neural crest migration, and skeletal development during embryogenesis. In the adult, versican acts as an inflammation "amplifier" and regulator of immune cell activation and cytokine production. Increased versican expression has been observed in a wide range of malignant tumors and has been associated with poor patient outcomes. The main sources of versican production in the tumor microenvironment include accessory cells (myeloid cells and stromal components) and, in some contexts, the tumor cells themselves. Versican has been implicated in several classical hallmarks of cancer such as proliferative signaling, evasion of growth suppressor signaling, resistance to cell death, angiogenesis, and tissue invasion and metastasis. More recently, versican has been implicated in escape from tumor immune surveillance, e.g., through dendritic cell dysfunction. Versican's multiple contributions to benign and malignant biological processes are further diversified through the generation of versican-derived bioactive proteolytic fragments (matrikines), with versikine being the most studied to date. Versican and versican-derived matrikines hold promise as targets in the management of inflammatory and malignant conditions as well as in the development of novel predictive and prognostic biomarkers.