Abstract LB-310: Changes in the gene expression profile of A375 human melanoma cells induced by over-expression of multifunctional pigment epithelium-derived factor

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.LB-310-LB-310
• Main Authors: Jimenez, Benilde, Orgaz, Jose L.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-LB-310

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 that PEDF prevents primary tumor growth and metastatic spread of human melanoma in mouse experimental models. Consistent with these observations, PEDF expression is lost at the late stages of melanoma progression, allowing melanoma cells to become angiogenic, migratory and invasive. PEDF's ability to modify the interplay between the host and tumor tissues strongly supports its use as a therapeutic agent for the treatment of metastatic melanoma. However, transition to the clinic requires a more detailed knowledge of the molecular mechanisms underpinning PEDF's activity. In this study we describe changes in the gene expression profile of A375 human melanoma cells induced by PEDF over-expression. PEDF modulated diverse categories of genes known to be involved in angiogenesis and migration. It downregulated cytokines like interleukin 8 and extracellular matrix proteins like collagen IV, while it upregulated fibronectin. Multiple transcripts previously described as contributing to the acquisition of malignant phenotype by melanoma were also diminished by PEDF over-expression, among which we validated galectin 3 and jagged 1. Additionally, PEDF downregulated S100β and melanoma inhibitory activity (MIA), which are widely used in the pathological diagnosis of melanoma. Interestingly, PEDF increased the expression of melanophilin and decreased rab27A, which are relevant targets for melanosome transport; suggesting that PEDF could directly impinge on melanocytic lineage-specific processes. Our study identifies new molecular targets and signaling pathways that may potentially contribute to determine PEDF's ability to restrict the aggressiveness of A375 human melanoma cells. 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 LB-310. doi:1538-7445.AM2012-LB-310