Journal of Clinical Toxicology
Open Access

Activation of FGF2-FGFR1 axis by visceral fat is responsible for malignant transformation of epithelial cells in mice kept on high fat diet

9^th Euro-Global Summit on Toxicology and Applied Pharmacology

June 22-24, 2017 Paris, France

Debrup Chakraborty, Blair Bullard and Jamie J Bernard

Michigan State University, USA

Posters & Accepted Abstracts: J Clin Toxicol

Abstract :

Increased adiposity plays a crucial role in the pathogenesis and prognosis of different types of cancers, especially in obese individuals. Epidemiological evidence suggests visceral adipose tissue (VAT) and high-fat diets (HFD) are associated with increased cancer risk however, the mechanism is not well understood. The aim of this study was to explore the factors in VAT that stimulate malignant transformation. We modeled visceral adiposity-stimulated malignant transformation using our novel ex vivo system of VAT-condition medium stimulated epithelial cell transformation (measured by growth in 3D cell culture model of soft agar) and our in vivo murine lipectomy model of ultraviolet light B (UVB)-induced, VAT promoted skin tumor formation. We found that VAT from mice and obese human donors stimulated malignant transformation of non-tumorigenic epithelial cells. Moreover, the VAT of obese mice fed a HFD [not VAT from low-fat diet (LFD) fed mice] stimulated malignant transformation. Furthermore, human VAT stimulated both skin and mammary epithelial cell transformation. The differences in VAT activity between LFD and HFD fed mice and human donors were associated with the levels of FGF2. Circulating levels of FGF2 were associated with non-melanoma tumor formation in vitro. Human and mouse VAT failed to stimulate transformation in FgfR1(-/-) cells and do not form tumors when injected in Nude mice in vivo. Collectively, our data show FGF2 released from VAT and its interaction with FGFR1 is a novel and potential direct path of VAT-enhanced tumorigenesis. Blocking the FGF2-FGFR1 axis in VAT of abdominally obese individuals may be an important cancer prevention strategy as well as an adjuvant therapy for improving outcomes following cancer diagnosis.

Biography :

Email: chakra40@msu.edu