Investigação da expressão e distribuição de moléculas de adesão celular no microambiente tumoral de melanoma

Abstract

Cutaneous melanoma is a skin cancer known for its high aggressiveness and metastatic potential, processes that are partly mediated by adhesion molecules present in the tumor microenvironment. This study evaluated the expression of six adhesion molecules in public datasets of murine and human melanoma, namely: ICAM-1, ICAM-2, NCAM-1, VCAM-1, PECAM-1, and MCAM. In the murine model (B16F10), a public single-cell RNA-seq database was used to analyze the distribution of these genes in the tumor microenvironment. In humans, the analysis was performed using the GEPIA platform, which integrates gene expression data from tumors in TCGA (The Cancer Genome Atlas) and normal tissues in GTEx (Genotype-Tissue Expression). In murine results, ICAM1 was widely expressed in malignant cells, cancer-associated fibroblasts (CAFs), dendritic cells, macrophages, and T lymphocytes. VCAM1 showed heterogeneous expression across cell types and, like NCAM1, reached maximum levels in CAFs. ICAM2, PECAM1, and MCAM were restricted to malignant cells. In the human profile, ICAM1, VCAM1, and MCAM were more highly expressed in tumors than in normal skin, whereas ICAM2 and PECAM1 showed divergent patterns between species. Segmented analysis revealed predominance of PECAM1 and MCAM in tumor cells and of ICAM1 and VCAM1 in CAFs, indicating a specific distribution among tumor microenvironment cell types. These findings suggest that ICAM-1, VCAM-1, and MCAM are conserved adhesion molecules and potential therapeutic targets, while the differences observed for ICAM2 and PECAM-1 indicate biological particularities that warrant further investigation. Future in-depth studies, including in vitro and in vivo analyses, as well as evaluation of their relationship with therapeutic response and prognosis, are needed to precisely delineate the role of these molecules in melanoma.