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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.

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


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.

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