Lipid Accumulation Promotes Tumorigenic Behaviour of Colorectal Cancer Cells.

Obesity and hyperlipidemia are risk factors for the development and progression of different types of cancer including colorectal cancer (CRC). The underlying mechanisms are only incompletely understood. The aim of this study was to assess the impact of hyperlipidemic conditions on tumorigenic behaviour of CRC cells and the effect of obesity on lipid metabolism in CRC tissues. Oleic acid complexed to albumin was added to the cell culture medium of human colon cancer cell lines HT29, Caco-2, HCT116, LoVo, SW480 and SW48. This led to a time- and dose-dependent uptake of oleate and triglyceride accumulation and increased expression of perilipin-2 (PLIN2), a structural component of lipid droplets and carnitine palmitoyltransferase 1 A (CPT1A), the key enzyme of beta-oxidation. Furthermore, proliferation, migratory activity and the expression of epithelial-mesenchymal transition (EMT) markers and the proinflammatory cytokine interleukin-8 (IL-8) were dose-dependently increased in CRC cells. In tumorous tissues of obese CRC patients, PLIN2 expression tended to be higher than in tissues of CRC patients with normal weight and immunohistological analysis showed a stronger PLIN2 immunosignal and Ki67-staining a higher proliferative index in CRC tissues of obese patients. Furthermore, we observed a significant correlation between PLIN2 and CPT1A expression in human CRC tissues and CRC patients with high PLIN2 or CPT1A expression showed a poorer overall and disease-free survival. In conclusion, our data indicate that fatty acid uptake promotes tumorigenicity of CRC cells. The exogenous uptake of fatty acids could be particularly important in obesity associated hyperlipidemia and herewith may be a critical factor by which obesity promotes CRC progression. Here, these findings support further evaluation of the structural protein PLIN2 as tumour marker as well as therapeutic target in CRC patients.