Abstract
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. 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 (crown-like 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. These studies provide the first in vitro demonstration of a parametrial fat tissue-induced transformation of an epidermal cell.
Highlights
Non-melanoma skin cancer is the most common neoplasm in the United States with over 2 million new cases diagnosed per year caused predominantly by exposure to UVA and UVB in sunlight, the most prevalent environmental carcinogen [1]
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
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 HFD, but not a LFD indicating that the parametrial fat tissue from mice fed a HFD played a role in skin carcinogenesis
Summary
Non-melanoma skin cancer is the most common neoplasm in the United States with over 2 million new cases diagnosed per year caused predominantly by exposure to UVA and UVB in sunlight, the most prevalent environmental carcinogen [1]. 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. These data suggested that the parametrial fat tissue from mice fed a HFD secretes tumorigenic substances that promote skin tumor formation. As the mouse Balb/C epidermal JB6 P+ cell line has been utilized as a well-characterized in vitro model for neoplastic transformation by tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) [10], to determine the differences between visceral fat tissue from mice fed either a HFD or LFD in carcinogenesis, we tested the effect of an aqueous filtrate made from parametrial fat tissue on the in vitro transformation of JB6 epidermal cells
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