In Vitro Modeling of Adipocyte Hypertrophy Identifies WNT5A and Chemerin as Potential Mediators of Obesity–Cancer Crosstalk

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with a five-year survival rate of only 12%. Obesity increases PDAC risk (relative risk 1.19–1.47) and is characterized by adipocyte hypertrophy, which alters adipokine secretion. Both WNT5A and chemerin are upregulated in PDAC and obesity; while WNT5A promotes oncogenesis, chemerin’s role remains unclear. This study developed an in vitro model of adipocyte hypertrophy to examine WNT5A and chemerin expression and their effects on PDAC. 3T3-L1 adipocytes were cultured for 18 days and treated with 2.5 nM TNF for 24h on day 17. Hypertrophic adipocytes showed twofold and fourfold increases in chemerin and WNT5A secretion, respectively. MIA-PaCa-2 cells exposed to conditioned media from hypertrophic adipocytes or to recombinant WNT5A or chemerin at concentrations secreted by hypertrophic adipocytes displayed no change in proliferation but showed significantly increased migration. These results highlight role of the adipose-tumour axis in PDAC.