Parametrial Fat Tissue from High Fat Diet-Treated SKH-1 Mice Stimulates Transformation of Mouse Epidermal JB6 CellsJamie J. Bernard1, You-Rong Lou1, Qing-Yun Peng1, Tao Li1, Priyal R. Vakil1, Ning Ding1, Jeffrey D. Laskin2, Zigang Dong3, Allan H.Conney1#, and Yao-Ping Lu1*
- *Corresponding Author:
- Dr. Yao-Ping Lu
Susan Lehman Cullman Laboratory for Cancer Research
Department of Chemical Biology, Ernest Mario School of Pharmacy
Rutgers, The State University of New Jersey, 164 Frelinghuysen Rd
Piscataway, NJ 08854, USA
E-mail: [email protected]
Received date: May 15, 2014; Accepted date: July 29, 2014; Published date: July 31, 2014
Citation: Bernard JJ, Lou YR, Peng QY, Li T, Vakil PR, et al. (2014) Parametrial Fat Tissue from High Fat Diet-Treated SKH-1 Mice Stimulates Transformation of Mouse Epidermal JB6 Cells. J Carcinog Mutagen 5:183 doi: 10.4172/2157-2518.1000183
Copyright: © 2014 Bernard JJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Our previous studies indicated that decreasing visceral adipose tissue by surgical removal of the parametrial fat pads inhibited UVB-induced carcinogenesis in SKH-1 mice fed a high fat diet (HFD), but not a low fat diet (LFD) indicating that the parametrial fat tissue from mice fed a HFD played a role in skin carcinogenesis.
Objective: In the present study, we sought to investigate how a HFD may influence the intrinsic properties of the parametrial fat tissue to influence UVB-induced skin tumor formation.
Methods and Results: Immunohistochemical staining, adipokine array, and flow cytometry showed that parametrial fat tissue from mice fed a HFD had a higher density of macrophage-fused dead adipocytes (crownlike structures), more adipokines, and stimulated the production of more reactive oxygen species compared with parametrial fat tissue from mice fed a LFD. These differences between parametrial fat tissue from mice fed a HFD and LFD were associated with their effect on the in vitro transformation of mouse epidermal JB6 cells. Our results indicated that fat tissue filtrate (an aqueous filtrate made from the parametrial fat pad) from mice fed a HFD enhanced the conversion of JB6 cells from an epithelial-like morphology to cells with a fibroblast-like morphology to a greater extent than fat tissue filtrate from mice fed a LFD. Studies indicated that the fibroblast-like cells had decreased levels of E-cadherin, increased levels of Twist as assayed by western blot. Fat tissue filtrate made from the parametrial fat tissue of mice fed a HFD had 160% more transforming activity than that from mice fed a LFD and formed malignant mesenchymal tumors in vivo.
Conclusion: These studies provide the first in vitro demonstration of a parametrial fat tissue-induced transformation of an epidermal cell.