Vascular endothelial profilin-1 drives a protumorigenic tumor microenvironment and tumor progression in renal cancer

Roughly 80,000 new cases of renal cell carcinoma (or kidney cancer) with estimated 15,000 deaths occur per year. Clear cell renal cell carcinoma is the most common subtype of renal cell carcinoma, accounting for over 75% of kidney cancer cases. Metastatic renal cell carcinoma patients also have a 5-year survival of less than 10% with median survival being around 13 months. A key characteristic of this type of tumor is its highly vascularized tumor microenvironment, meaning that the environment is rich in blood vessels. This is due to loss of a number of genes such as Von-Hippel Lindau, or VHL, which plays a major role in initiation as well as progression of this disease. Outside of surgical removal of the primary tumor, anti-angiogenic therapies such as those targeting VEGF to promote vascular normalization are the first line therapy for renal cell carcinoma patients. Almost all these patients, however, develop resistance and progression of drug-resistant disease. In our recent study, we explored the role of actin-binding protein profilin-1 in regulation of renal cell carcinoma. We show that profilin-1 expression is higher in advanced stage renal cell carcinoma and correlated to lower patient survival. In addition, we note that increased profilin-1 expression is found mainly in tumor-associated vascular endothelial cells (the cells lining blood vessels) in human clear cell renal cell carcinoma patients. We have demonstrated previously that profilin-1 is important for many fundamental cellular processes such as cell migration, proliferation, and angiogenesis (new blood vessel formation). This study shows for the first-time proof of direct causal relationship between vascular endothelial profilin-1 dysregulation, alternations in tumor microenvironment, and disease progression in kidney cancer. This work also further justifies targeting profilin-1 for therapeutic benefit in kidney cancer.