Immunosuppressive Agent May Promote Tumor Growth
Cyclosporine increases tumor size and enhances tumor angiogenesis in an in vivo model
MONDAY, July 21 (HealthDay News) -- While calcineurin inhibitors are effective immunosuppressive agents that inhibit allograft rejection, they may actually promote tumor growth, according to an article published in the July 15 issue of Cancer Research.
Aninda Basu, Ph.D., of Children's Hospital Boston, and colleagues performed a series of in vitro and in vivo studies to determine whether cyclosporine, a calcineurin inhibitor and common immunosuppressive agent, promotes human cancer cell growth through expression of vascular endothelial growth factor (VEGF). In in vitro studies, the effect of cyclosporine on VEGF expression was measured. In vivo, investigators injected human cancer cells into mice with fully major histocompatibility complex mismatched cardiac transplants and treated with cyclosporine and measured tumor size.
In the in vitro studies, cyclosporine treatments increased expression of a number of different VEGF factors. In the in vivo studies, tumor size increased with therapeutic doses of cyclosporine along with increased VEGF mRNA expression and tumor angiogenesis. However, when a blocking anti-VEGF antibody was administered, cyclosporine-mediated tumor growth was inhibited.
"Our in vitro and in vivo studies in this report clearly show the role of overexpressed VEGF in the development of cyclosporin-induced post-transplantation cancer," the authors write. "Targeting the pathways that promote VEGF overexpression in response to calcineurin inhibitors might serve as novel therapeutics for the prevention and treatment of post-transplantation cancer."