Abstract
Abstract The stromal cell-derived factor-1α SDF-1α (CXCL12)/CXCR4 axis has a critical role, particularly in renal cancer where CXCR4 expression has been linked to poor prognosis. Histone deacetylase inhibitors (HDIs) exert antitumor effects by targeting both histone and nonhistone proteins affecting cell migration, apoptosis, cell proliferation and angiogenesis. Thus, the aim of the present work was to evaluate the effects of the HDIs apicidin, vorinostat, MS-275 and romidepsin on the expression and function of CXCR4 in human cancer cell lines including renal, non-small cell lung, breast, colon and glioma cell lines. After treatment with romidepsin or apicidin, CXCR4 mRNA expression increased 12-fold in UOK121 and 2.5-fold in UOK143 renal cancer cell lines; treatment with vorinostat or MS-275 yielded similar effects. CXCR4 induction was also observed in H460 non-small cell lung cancer cells, and SF-295 glioblastoma cells, but not in MCF-7 breast cancer cells or SW620 colon cancer cells. To evaluate the corresponding CXCR4 functional increase, CXCL12-induced ERK1/2, STAT-3, and c-SRC activation and cell migration were examined in UOK121, SF295 and H460 cells. In general, the HDIs increased pERK1/2, while reducing pSTAT-3 and pSRC. Following CXCL12 pERK1/2 induction was maintained but STAT3 and SRC phosphorylation was impaired. These findings resulted in reduced basal and CXCL12-mediated cell migration. In conclusion, HDIs up-regulated CXCR4 mRNA expression but impaired signalling cascades CXCL12-dependent on STAT3 and c-SRC, suggesting a role for HDI in delaying or preventing metastatic process in solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2633. doi:10.1158/1538-7445.AM2011-2633
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