Adipocyte-derived CXCL10 in obesity promotes the migration and invasion of ovarian cancer cells

J Ovarian Res. 2024 Dec 19;17(1):245. doi: 10.1186/s13048-024-01568-0.

Abstract

Background: As a widespread epidemic, obesity poses a significant risk to health and leads to physiological abnormalities, including diabetes mellitus and inflammation. Obesity-induced inflammation can accelerate the development of various cancers; however, the role of obesity in the migration of ovarian carcinoma is still unclear.

Results: Twenty-four commonly upregulated genes were identified from single-cell RNA sequencing datasets of both ovarian carcinoma and adipose tissue of obese humans, with the chemokine CXCL10 showing a significant increase in adipose tissues associated with obesity. And CXCL10 treated primed macrophages exhibit both direct and indirect effects on the proliferation, apoptosis, migration, and invasion of ovarian adenocarcinoma cells. The treatment of CXCL10 on the SKOV3 cells enhances FAK expression and phosphorylation, thereby accelerating the migration and invasion of ovarian cancer cells. Conditioned medium-derived from CXCL10-treated THP-1 cells significantly promoted ovarian cancer cell migration and invasion, which may be attributed to the increased expression of C1QA, C1QC, CCL24, and IL4R in macrophages.

Conclusions: Obesity exacerbates the production of CXCL10 from adipose tissues in obese women. CXCL10 is a key hub factor between developments of ovarian cancer and adipose tissues in obese. Targeting adipose-derived CXCL10 or its downstream macrophages may be a potential strategy to alleviate ovarian cancer accompanied by obesity.

Keywords: Adipose tissue; CXCL10; Macrophage; Obesity; Ovarian carcinoma.

MeSH terms

  • Adipocytes / metabolism
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Chemokine CXCL10* / genetics
  • Chemokine CXCL10* / metabolism
  • Female
  • Humans
  • Macrophages / metabolism
  • Neoplasm Invasiveness
  • Obesity* / complications
  • Obesity* / metabolism
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology

Substances

  • Chemokine CXCL10
  • CXCL10 protein, human