Cancer‑associated adipocytes exhibit distinct phenotypes and facilitate tumor progression in pancreatic cancer.

Adipocyte infiltration in pancreatic cancer (PC) has been demonstrated to be independently associated with PC risk and an active contributor to tumor progression. However, to date, little is known about these unique pancreatic tumorsurrounding adipocytes, or their response to cancer cells. The present study utilized an in vitro indirect coculture model in which the phenotypic changes of adipocytes following exposure to PC cells were directly observed. RNAsequencing was performed on 3T3L1 adipocytes cultured with or without Panc1 cancer cells, and significant changes were identified at the transcriptional level. In terms of delipidation and the impaired function of glucose and lipid metabolism, coculture with tumor cells resulted in an altered metabolic phenotype in mature adipocytes. In cocultured adipocytes, the appearance of fibroblastlike cells was observed, and the mesenchymal cell differentiation pathway was enriched following the integrated analysis into the transcriptome. In addition, reverse transcriptionquantitative PCR analyses of cocultured adipocytes revealed a loss in gene expression of mature adipocyte markers, and a gain in gene expression of fibroblastspecific markers. It was also confirmed that newly generated cancerassociated adipocytes could facilitate the invasive capacities of the tumor, and may contribute to PC stromal remodeling. The present study supports a novel concept that reprogramming of stromal adipocytes orchestrated by PC cells may generate cancerassociated adipocytes with activated phenotypes, which may ultimately drive pancreatic tumor progression.