Adipocytes promote pancreatic cancer migration and invasion through fatty acid metabolic reprogramming.

Content Provider	Europe PMC
Author	Cai, Zhiwei Li, Yang Ma, Mingjian Wang, Longxiang Wang, Hongwei Liu, Meng Jiang, Chongyi
Copyright Year	2023
Abstract	Locally advanced and metastatic pancreatic cancer (PC) frequently grows in adipose tissue and has a poor prognosis. Although adipose tissue is largely composed of adipocytes, the mechanisms by which adipocytes impact PC are poorly understood. Using an in vitro coculture model, it was shown that adipocytes promoted tumor progression, and an intricate metabolic network between PC cells and adipocytes was identified and elucidated. First, the proteome of Panc-1 PC cells cultured with or without mature adipocytes was identified. This revealed activated hypoxia signaling in cocultured Panc-1 cells, which was confirmed by the increased expression of factors downstream of hypoxia signaling, such as ANGPTL4 and glycolytic genes, as determined by reverse transcription-quantitative PCR and western blot analysis. In addition, it was demonstrated that coculture with cancer cells activated STAT3 and induced an insulin-resistant phenotype in adipocytes. Furthermore, enhanced fatty acid β-oxidation and increased lipid droplets (LDs) were observed in the cocultured cancer cells. In contrast, downregulated lipid metabolism and a decrease in the size of LDs were found in cocultured adipocytes. Finally, it was shown that the increase in LDs contributed to the increased metastatic capacity of the cocultured PC cells. These data demonstrated that interrupting the mechanisms of lipid uptake from adipocytes in the microenvironment may offer a potential strategy for attenuating PC metastasis.
ISSN	1021335X
Journal	Oncology Reports
Volume Number	50
PubMed Central reference number	PMC10285608
Issue Number	1
PubMed reference number	37264956
e-ISSN	17912431
DOI	10.3892/or.2023.8578
Language	English
Publisher	D.A. Spandidos
Publisher Date	2023-06-02
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Cai et al.
Subject Keyword	pancreatic cancer adipocyte tumor microenvironment metabolism fatty acid
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology