Caveolin‐1 increases glycolysis in pancreatic cancer cells and triggers cachectic states

In pancreatic cancer, autocrine insulin‐like growth factor‐1 (IGF‐1) and paracrine insulin stimulate both IGF‐1 receptor (IGF1R) and insulin receptor (IR) to increase tumor growth and glycolysis. In pancreatic cancer patients, cancer‐induced glycolysis increases hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis and, thereby, causes cancer cachexia. As a protein coexisting with IGF1R and IR, caveolin‐1 (cav‐1) may be involved in pancreatic cancer‐induced cachexia. We undertook the present study to test this hypothesis. Out of wild‐type MiaPaCa2 and AsPC1 human pancreatic cancer cell lines, we created their stable sub‐lines whose cav‐1 expression was diminished with RNA interference or increased with transgene expression. When these cells were studied in vitro, we found that cav‐1 regulated IGF1R/IR expression and activation and also regulated cellular glycolysis. We transplanted the different types of MiaPaCa2 cells in growing athymic mice for 8 weeks, using intact athymic mice as tumor‐free controls. We found that cav‐1 levels in tumor grafts were correlated with expression levels of the enzymes that regulated hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis in the respective tissues. When the tumors had original or increased cav‐1, their carriers’ body weight gain was less than the tumor‐free reference. When cav‐1 was diminished in tumors, the tumor carriers’ body weight gain was not changed significantly, compared to the tumor‐free reference. In conclusion, cav‐1 in pancreatic cancer cells stimulated IGF1R/IR and glycolysis in the cancer cells and triggered cachectic states in the tumor carrier.