Uptake of fatty acids and lipid accumulation promote prometastatic characteristics of colorectal cancer cells

The liver is the most common site of colorectal cancer (CRC) metastasis, and hepatic metastasis is the primary driver of disease-specific mortality for patients with CRC. Obesity is frequently associated with hyperlipidemia and is a risk factor for development of hepatic metastases, however the underlying mechanisms are incompletely understood.

The aim of this study was to assess the impact of hyperlipidemic conditions on prometastatic behaviour of CRC cells and to analyze the effects of obesity and lipid accumulation in human CRC tissues and liver metastases. CRC cell lines were incubated with free fatty acids (FFA) complexed to albumin to mimic hyperlipidemia. This led to an uptake of FFA, enhanced triglyceride (TAG) accumulation as well as CPT1 expression and beta-oxidation, known to promote (hepatic) CRC metastasis. These metabolic changes significantly induced proliferation, migratory activity as well as expression of proinflammatory genes. Expression of the lipid droplet associated protein perilipin 2 (PLIN2) was identified as a surrogate marker for TAG accumulation in CRC cells. Analysis of human CRC tissues showed higher PLIN2 expression in obese compared to lean patients, and high PLIN2 expression correlated with poor overall survival. Moreover, we detected high PLIN2 and CPT1 expression in hepatic metastases of CRC patients.

Our data indicate that hyperlipidemic conditions promote prometastatic behaviour of CRC cells and that PLIN2 expression might serve as a prognostic marker for hepatic CRC metastasis. Furthermore, interference with exogenic high-fat supply could be a promising strategy to prevent and treat liver metastasis of CRC patients.

Publication History

Article published online:
20 January 2025