Chemokine and Cytokine Receptor Signatures Associated with Pulmonary Endothelial-Conditioned Melanoma Invasion
- 1Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4028 Debrecen, Hungary
- 2HUN-REN-UD Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
- 3Doctoral School of Health Sciences, University of Debrecen, 4032 Debrecen, Hungary
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.
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BibTeX
@article{koroknai2026chemokine,
title = {{Chemokine and Cytokine Receptor Signatures Associated with Pulmonary Endothelial-Conditioned Melanoma Invasion}},
author = {Viktória Koroknai and István Szász and Marwa Hamdan and Ágnes Berecz and Margit Balázs},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101510},
url = {https://www.mdpi.com/2218-273X/16/10/1510},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chemokine and Cytokine Receptor Signatures Associated with Pulmonary Endothelial-Conditioned Melanoma Invasion
AU - Viktória Koroknai
AU - István Szász
AU - Marwa Hamdan
AU - Ágnes Berecz
AU - Margit Balázs
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101510
UR - https://www.mdpi.com/2218-273X/16/10/1510
AB - 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.
SN - 2218-273X
ER -