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Impact of diet-induced obesity on melanoma progression: "in vitro" studies

(2025)

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Lecomte, Julie_05431900_2025.pdf
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Abstract
Obesity is a global health issue and well-established risk factor for several cancers, particularly those of the digestive and hormonal systems. While the association between obesity and melanoma remains controversial, emerging evidence suggests a possible link with increased tumor aggressiveness. This study investigates how diet induced obesity may affect melanoma progression, using both in vitro and ex vivo approaches. Conditioned media were collected from subcutaneous and epididymal adipose tissue explants of mice fed either a normal diet (ND) or a high fat diet (HFD), with or without tumor. These conditioned media were then applied to melanoma cell lines (YUMM1.7 and YUMMER1.7) to measure cell proliferation in vitro. In parallel, ex vivo experiments were conducted using quantitative PCR to examine the inflammatory profile of the resected tumors, of adipose tissue explants and of subcutaneous adipose tissues samples. Our in vitro experiments showed that conditioned media derived from mouse adipose tissue stimulated melanoma cell proliferation regardless of the diet, with a lack of distinction between the effect of conditioned media derived from obese and normal mice. In addition, tumors resected from HFD obese mice did not show significant differences in inflammatory gene expression compared to tumors resected from ND lean mice. In contrast, ex vivo gene expression analyses in subcutaneous adipose tissues revealed that obesity led to an increase in pro-inflammatory marker levels (TNFα, MCP1, F4/80), independent of tumor presence. These findings point towards the fact that even though obesity promotes tumor growth in vivo, the adipose tissue secretory function alone is not sufficient to replicate this effect in vitro. However, chronic inflammation and systemic mechanisms may be responsible for obesity-driven acceleration of melanoma growth. This research brings new perspectives into the complex relationship between metabolic condition and cancer progression.