Abstract 557: Galectin-3 binding protein produced by neuroblastoma cells stimulates the expression of interleukin-6 in bone marrow mesenchymal cells

Abstract

There is recent evidence that bone marrow-derived mesenchymal cells (BMMC) play an important role in bone metastasis in several cancers, including myeloma and neuroblastoma. We previously reported that in neuroblastoma these cells are a source of interleukin-6 (IL-6) that promotes the growth and survival of neuroblastoma cells and bone degradation. We have recently isolated and identified Galectin-3 binding protein (Gal-3BP) as a soluble factor produced by a neuroblastoma cell line as a factor upregulating the production of IL-6 by BMMC. Here we document the production of Gal-3BP in several neuroblastoma cell lines, in particular those without MYCN amplification that correlates with their ability to induce the production of IL-6 in BMMC. The stimulation of IL-6 by Gal-3BP is mediated by Gal-3, a multifunctional glycoprotein that binds Gal-3BP and is present in BMMC. It is also dependent on the activation of the Ras/Raf/MEK/ERK1/2 pathway by Gal-3BP/Gal-3 and is blocked by the ERK1/2 inhibitor PD980559. Transcriptional activation of IL-6 by Gal-3BP/Gal-3 requires a 115 bp region (−97 to −212) in the IL-6 promoter that contains recognition motifs for a cAMP responsive element binding protein (CREB) and a CCAAT/enhancer binding protein (C/EBP). The expression of Gal-3BP was also examined by immunohistochemistry in 38 primary neuroblastoma tumors with (n=9) and without (n=29) MYCN amplification. This analysis revealed that Gal-3BP is paradoxically more abundant in MYCN non-amplified tumors. This unanticipated observation suggests a significant difference in the Gal-3BP/Gal-3/IL-6 pathway between subgroups of neuroblastoma tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 557.