Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients

Olatz Crende, Marianna Sabatino, María Valcárcel, Teresa Carrascal, Pia Riestra, Jose A. López-Guerrero, Eduardo Nagore, Susanna Mandruzzato, Ena Wang, Francesco M. Marincola, Fernando Vidal-Vanaclocha

Research output: Contribution to journalArticle

Abstract

IL-18 is an immune-stimulating cytokine that promotes experimental melanoma metastasis via vascular endothelial growth factor (VEGF)-induced very late antigen (VLA)-4. We studied genes associated with the ability of melanoma cells to allow metastasis under IL-18 effects, and we verified their expression in metastatic lesions from patients with melanoma. Human melanoma cell lines with and without the IL-18 receptor (IL-18R)/VEGF/VLA-4-expressing phenotype were identified, and their metastatic potential was studied in nude mice. RNA from untreated and IL-18-treated melanoma phenotypes was hybridized to a cDNA microarray, and their signature genes were studied. RNA from primary and metastatic lesions from patients with melanoma was hybridized to a cDNA microarray to identify lesions with the transcript patterns of melanoma cells with and without the IL-18R/VEGF/VLA-4 phenotype. IL-18R/VEGF/VLA-4-expressing A375 and 1182 melanoma cells produced a higher metastasis number than 526 and 624.28 melanoma cells, not using this prometastatic pathway. Melanoma cells with and without the IL-18R/VEGF/VLA-4 phenotype had distinct transcript patterns. However, the type I transcriptional cluster, including cutaneous and lymph node metastases, but not the type II cluster, not including cutaneous metastases, had signature genes from IL-18-treated melanoma cells with, but not without, the IL-18R/VEGF/VLA-4 phenotype. Metastatic melanoma lesions with and without IL-18-dependent genes were identified, suggesting that melanoma metastasis developed via inflammation-dependent and inflammation-independent mechanisms. Signature genes from melanomas with and without the IL-18R/VEGF/VLA-4 phenotype may serve as diagnostic biomarkers of melanoma predisposition to prometastatic effects of IL-18.

Original languageEnglish
Pages (from-to)69-82
Number of pages14
JournalAmerican Journal of Pathology
Volume183
Issue number1
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Crende, O., Sabatino, M., Valcárcel, M., Carrascal, T., Riestra, P., López-Guerrero, J. A., Nagore, E., Mandruzzato, S., Wang, E., Marincola, F. M., & Vidal-Vanaclocha, F. (2013). Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients. American Journal of Pathology, 183(1), 69-82. https://doi.org/10.1016/j.ajpath.2013.03.026