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- W4377097103 abstract "PURPOSE: Recent studies in Ovarian, Breast, and Endometrial cancer suggest that there is a correlation between adipocytes and tumorigenesis, leading to malignancy. In an activated state, adipocytes may release adipokines which are known to promote tumor development. Increased adipocyte deposition in subcutaneous tissue also enhances the metastatic ability of melanoma. Our study examines whether decreasing adipogenesis using Piloglitzone, may decrease skin melanoma tumorigenesis. METHODS:AdipoqCre transgenic driver mice were crossed to R26mTmG reporter mice to generate AdipoqCre;ROSA26mTmG mice, in which mature adipocytes (Adipoq/adiponectin-expressing cells) express green fluorescent protein (GFP), and all other cells express a red fluorescent protein (RFP). B16 mouse melanoma cells (50, 000 cells/ site) were injected subdermally into the dorsum of AdipoqCre;ROSA26mTmG mice, with and without subdermal injections of Piloglitzone. Melanoma and surrounding tissue were harvested at postoperative day-10 (POD10) and underwent immunofluorescent staining for fibroblast (collagen type IV/col-IV, alpha-smooth muscle actin/a-SMA) and adipocyte (perilipin) cell markers. Tumor size was quantified at POD10. FACS analysis was also used to quantify GFP+ adipocyte infiltration at POD10. RESULTS: We identified a significant decrease in melanoma tumor size following injection of Piloglitzone at POD10 (*p<0.05). Adiponectin-lineage-positive cells (GFP+) within the melanoma was also significantly reduced following Piloglitzone injections by FACS. The GFP+ cells that infiltrated the melanoma injury without Piloglitzone exhibited upregulation of fibrotic markers including col-IV and α-SMA, and downregulation of adipocyte markers including perilipin, indicating conversion of adipocytes into pro-fibrotic fibroblasts. CONCLUSION: Our study demonstrates that adipocytes undergo conversion to pro-fibrotic fibroblasts in response to melanoma tumor formation. Targeted adipocyte ablation using piloglitzone resulted in reduced tumor burden, suggesting that adipocyte-derived fibroblasts may be important in melanoma tumor progression." @default.
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- W4377097103 date "2023-05-01" @default.
- W4377097103 modified "2023-09-26" @default.
- W4377097103 title "SP01. Piloglitzone Decreases Adipogenisis Leading to Melanoma Skin Tumour Suppression" @default.
- W4377097103 doi "https://doi.org/10.1097/01.gox.0000938348.89813.61" @default.
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