Changes in the gene expression profile of A375 human melanoma cells induced by overexpression of multifunctional pigment epithelium-derived factor

作者: Jose L. Orgaz , Alberto Benguria , Cristina Sanchez-Martinez , Omar Ladhani , Olga V. Volpert

DOI: 10.1097/CMR.0B013E32834495C3

关键词: Angiogenesis inhibitorMelanoma inhibitory activityCancer researchRegulation of gene expressionGalectin-3Melanosome transportMelanomaBiologyAngiogenesisPEDF

摘要: Pigment epithelium-derived factor (PEDF) is a broad-spectrum angiogenesis inhibitor that displays potent anti-metastatic activity in multiple tumor types. We have previously shown PEDF prevents primary growth and metastatic spread of human melanoma mouse experimental models. Consistent with these observations, expression lost at the late stages progression, allowing cells to become angiogenic, migratory invasive. PEDF’s ability modify interplay between host tissues strongly supports its use as therapeutic agent for treatment melanoma. However, transition clinic requires more detailed knowledge molecular mechanisms underpinning activity. In this study we describe changes gene profile A375 induced by over-expression. modulated diverse categories genes known be involved migration. It downregulated cytokines like interleukin 8 extracellular matrix proteins collagen IV, while it upregulated fibronectin. Multiple transcripts described contributing acquisition malignant phenotype were also diminished over-expression, among which validated galectin 3 jagged 1. Additionally, S100β inhibitory (MIA), are widely used pathological diagnosis Interestingly, increased melanophilin decreased rab27A, relevant targets melanosome transport; suggesting could directly impinge on melanocytic lineage-specific processes. Our identifies new signaling pathways may potentially contribute determine restrict aggressiveness cells.

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