Work

Chemokine and Cytokine Receptor Signatures Associated with Pulmonary Endothelial-Conditioned Melanoma Invasion

Year: 2026

Type: article

Abstract: Background: Pulmonary endothelial cells are increasingly recognized as active regulators of organ-specific metastasis; however, the mechanisms by which they influence melanoma invasion remain incompletely understood. Methods: Six primary melanoma-derived cell lines were first assessed for their invasive responses to HPMEC-conditioned medium. In a separate HPMEC co-culture invasion model, invasive and non-invasive melanoma subpopulations were isolated and analyzed for the expression of 88 chemokine and cytokine receptor genes. Candidate receptors were subsequently validated in primary melanoma tissues (n = 15), while their corresponding ligands were analyzed in patient plasma samples (n = 30). Results: HPMEC-conditioned medium enhanced invasion in half of the melanoma cell lines. Exploratory receptor-expression analyses identified candidate genes, including CCR2, IL11RA, IL15RA, TNFRSF11B, and TNFRSF12A, with expression patterns potentially associated with the observed invasive responses, while CCR4 expression was consistently elevated in all invasive subpopulations. In an exploratory analysis of a small primary melanoma tissue cohort, CCR2 and TNFRSF11B expression was significantly higher in tumors from patients with lung metastases, while IL11RA expression was upregulated compared with that in non-metastatic tumors. Melanoma cells consistently induced endothelial IL-8 expression, whereas plasma concentrations of the corresponding ligands did not differ significantly between patient groups. Conclusions: The elevated expression of CCR2, IL11RA, and TNFRSF11B observed in primary melanomas associated with lung metastases suggests that these factors may contribute to the development or progression of pulmonary metastases. These findings highlight the potential role of bidirectional communication between endothelial cells and melanoma cells in metastatic progression.

Source: Biomolecules

DOI: 10.3390/biom16101510

Authors: Viktória Koroknai, István Szász, Marwa Hamdan, Ágnes Berecz, Margit Balázs

Institution: University of Debrecen

Language: English

Topic: Chemokine receptors and signaling

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258