Versican is a proteoglycan, a protein with attached sugar chains. It serves as a significant component of the extracellular matrix, the complex network of molecules providing structural and biochemical support to cells within tissues. It is widespread throughout the body, important for maintaining tissue integrity and function. Its interactions are central to numerous biological processes.
The Nature of Versican
Versican is classified as a chondroitin sulfate proteoglycan, belonging to the aggrecan/lectican family of molecules. Its basic structure includes a core protein to which long chains of chondroitin sulfate glycosaminoglycans (GAGs) are attached. These GAG chains are responsible for its ability to bind water, contributing to the hydrated and loose nature of the extracellular matrix.
It is found in the extracellular matrix of connective tissues, blood vessels, and the central nervous system. The human gene for versican, known as VCAN, can produce at least four distinct isoforms: V0, V1, V2, and V3. These different forms arise from alternative splicing of the VCAN gene, leading to variations in the size of the core protein and the number of attached GAG chains.
Versican’s Essential Roles in Healthy Tissues
Versican plays a role in the development and maintenance of healthy tissues. It is involved in processes like tissue development and morphogenesis, guiding embryonic cell migration crucial for heart formation and the path of neural crest cells. Its contribution to a loose and hydrated matrix supports key events during development.
The molecule also influences cellular behaviors, including cell adhesion, proliferation, and migration. By interacting with cells or other associated molecules, versican helps regulate these processes, which are important for tissue organization and repair. Furthermore, versican contributes to maintaining tissue integrity and is involved in normal wound healing and tissue repair.
Versican’s Contribution to Disease Progression
Altered levels or forms of versican are observed in various pathological conditions, where they contribute to disease progression. In cancer, for instance, increased expression of versican is linked to cancer aggressiveness, promoting tumor growth, invasion, and metastasis. It can create a permissive microenvironment that supports cancer cell spread and interacts with growth factors to facilitate tumor development.
Versican is also implicated in cardiovascular diseases, such as atherosclerosis and plaque formation. Its presence in blood vessels can promote extracellular lipoprotein retention, suggesting a role in lipid accumulation, inflammation, and blood clot formation. During inflammatory conditions, versican levels can increase, forming stable scaffolds with other extracellular matrix components like hyaluronan. These scaffolds can act as “landing strips” for inflammatory cells, facilitating their invasion into tissues and contributing to inflammation.
Versican as a Biological Indicator
The presence, levels, or specific forms of versican can serve as indicators of disease activity or progression. Changes in its expression are observed in various pathologies, including cardiovascular disease, lung disease, autoimmune conditions, and several cancers. For example, increased versican expression has been noted in breast, brain, ovarian, gastrointestinal, and prostate cancers, as well as melanoma.
Different versican isoforms or cleaved products can exhibit distinct or even opposing effects in various disease contexts. Fragments of versican, such as versikine, can act as damage-associated molecular patterns (DAMPs), interacting with immune and non-immune cells to stimulate the release of pro- and anti-inflammatory cytokines. These changes provide insights into ongoing pathological processes.