Abstract
Abstract BACKGROUND: The identification of proteins responsible for tumor development and regulation is of great value. In this study, we aimed to identify novel functional proteins associated with tumor progression in malignant melanoma. MATERIAL AND METHODS: The proteins extracted from malignant melanoma and normal skin tissue were labeled with iTRAQ reagent and performed a quantitative mass spectrometric analysis using nano LC-MS/MS system. The detected protein expression and localization in cutaneous malignant melanoma tissue was confirmed by immunohistochemistry. Human melanoma cell line (Mewo) was subcutaneously injected into Rag2-/- mice and POSTN-/-Rag2-/-mice, thereafter implanted tumor growth was compared. RESULTS: Among 1314 identified proteins, 118 proteins were increased more than 5.0-fold and 37 proteins were decreased <0.5-fold in malignant melanoma compared to normal tissue. In these proteins, we found significant upregulation of an extracellular matrix protein, periostin (POSTN). POSTN expression was robustly induced in fibroblast cultured with Mewo and evident on the stroma of advanced melanoma tissue, suggesting the importance of interaction of these cells. As an assessment of functional implication in POSTN in malignant melanoma, we observed significant increase in melanoma cell number in the treatment with recombinant POSTN. Moreover, tumor growth in POSTN-/-Rag2-/- mice was significantly suppressed compared with that in Rag2-/- mice.CONCLUSIONS: We newly identified upregulation of POSTN expression in malignant melanoma tissue. POSTN was induced in the co-culture of fibroblast with melanoma cell and showed the growth promoting effect. These results indicate that periostin might be a potential therapeutic target in malignant melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1275. doi:1538-7445.AM2012-1275
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