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Oncogene. 2017 Nov 30;36(48):6668-6679. doi: 10.1038/onc.2017.278. Epub 2017 Aug 7.

Fibroblast growth factor receptor is a mechanistic link between visceral adiposity and cancer.

Author information

1
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
2
Division of Surgical Oncology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
3
Section of Plastic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
4
Summit Medical4 Group, Livingston, NJ, USA.
5
Office for the Vice President for Research and Graduate Studies, Michigan State University, East Lansing, MI, USA.
6
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.

Abstract

Epidemiological evidence implicates excess adipose tissue in increasing cancer risk. Despite a steeply rising global prevalence of obesity, how adiposity contributes to transformation (stage a non-tumorigenic cell undergoes to become malignant) is unknown. To determine the factors in adipose tissue that stimulate transformation, we used a novel ex vivo system of visceral adipose tissue (VAT)-condition medium-stimulated epithelial cell growth in soft agar. To extend this system in vivo, we used a murine lipectomy model of ultraviolet light B-induced, VAT-promoted skin tumor formation. We found that VAT from mice and obese human donors stimulated growth in soft agar of non-tumorigenic epithelial cells. The difference in VAT activity was associated with fibroblast growth factor-2 (FGF2) levels. Moreover, human and mouse VAT failed to stimulate growth in soft of agar in cells deficient in FGFR-1 (FGF2 receptor). We also demonstrated that circulating levels of FGF2 were associated with non-melanoma tumor formation in vivo. These data implicate FGF2 as a major factor VAT releases to transform epithelial cells-a novel, potential pathway of VAT-enhanced tumorigenesis. Strategies designed to deplete VAT stores of FGF2 or inhibit FGFR-1 in abdominally obese individuals may be important cancer prevention strategies as well as adjuvant therapies for improving outcomes.

PMID:
28783178
PMCID:
PMC5709202
DOI:
10.1038/onc.2017.278
[Indexed for MEDLINE]
Free PMC Article

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