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

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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
Externally publishedYes

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Interleukin-18
Melanoma
Interleukin-18 Receptors
Integrin alpha4beta1
Vascular Endothelial Growth Factor A
Genes
Neoplasm Metastasis
Phenotype
Oligonucleotide Array Sequence Analysis
RNA
Inflammation
Skin
Experimental Melanomas
Nude Mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Crende, O., Sabatino, M., Valcárcel, M., Carrascal, T., Riestra, P., López-Guerrero, J. A., ... 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

Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients. / Crende, Olatz; Sabatino, Marianna; Valcárcel, María; Carrascal, Teresa; Riestra, Pia; López-Guerrero, Jose A.; Nagore, Eduardo; Mandruzzato, Susanna; Wang, Ena; Marincola, Francesco M.; Vidal-Vanaclocha, Fernando.

In: American Journal of Pathology, Vol. 183, No. 1, 07.2013, p. 69-82.

Research output: Contribution to journalArticle

Crende, O, Sabatino, M, Valcárcel, M, Carrascal, T, Riestra, P, López-Guerrero, JA, Nagore, E, Mandruzzato, S, Wang, E, Marincola, FM & Vidal-Vanaclocha, F 2013, 'Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients', American Journal of Pathology, vol. 183, no. 1, pp. 69-82. https://doi.org/10.1016/j.ajpath.2013.03.026
Crende, Olatz ; Sabatino, Marianna ; Valcárcel, María ; Carrascal, Teresa ; Riestra, Pia ; López-Guerrero, Jose A. ; Nagore, Eduardo ; Mandruzzato, Susanna ; Wang, Ena ; Marincola, Francesco M. ; Vidal-Vanaclocha, Fernando. / Metastatic lesions with and without interleukin-18-dependent genes in advanced-stage melanoma patients. In: American Journal of Pathology. 2013 ; Vol. 183, No. 1. pp. 69-82.
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