Melanoma and subcutaneous adipose tissue: Role of peritumoral adipokines in disease characterization and prognosis

Abstract

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF‐α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF‐α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

The Effect of Body Mass Index on Melanoma Biology, Immunotherapy Efficacy, and Clinical Outcomes: A Narrative Review

“…Increases in leptin and resistin encourage the growth and spread of melanoma cells and also alter the tumor microenvironment (TME) [20,21]. Kulkarni et al (2021) and Molinelli et al (2023) expanded on the topic by discussing the inflammatory and metabolic disturbances caused by obesity, emphasizing the dysregulation of adipose tissue and the emission of inflammatory and tumor-promoting adipokines [22,23]. Talib et al (2023) highlighted chronic inflammation, insulin resistance, and hormonal imbalances as key factors through which obesity promotes carcinogenesis [13] (Figure 1).…”

“…On the one hand, obesity promotes the proliferation of melanoma cells and may hinder the efficacy of traditional treatments, such as chemotherapy, through the action of obesity-associated adipokines like leptin and resistin. These substances not only accelerate melanoma cell growth but also modify the TME, creating conditions that favor tumor growth and resistance to therapy [ 19 , 20 , 21 , 22 , 23 ]. On the other hand, the altered immune landscape associated with obesity, characterized by impaired function and increased counts of dendritic cells and T cells, paradoxically seems to enhance the effectiveness of immunotherapies [ 12 ].…”

Alterations in Plasma Lipid Profiles Associated with Melanoma and Therapy Resistance

“…Several lines of evidence implicate the dysregulation of lipid metabolism in melanoma progression and therapy resistance [17]. Subcutaneous adipose tissue and released adipokines were suggested to promote melanoma growth [18]. Melanoma cells were shown to be able to take up lipids from extracellular vesicles released by stromal adipocytes or from aged fibroblasts by fatty acid transport protein (FATP) and use those to survive upon targeted therapy [19][20][21].…”