Abstract B3: CD24 affects tumor cell properties and cytokine secretion in a STAT3-dependent fashion

CD24 is a glycosyl-phosphatidylinositol (GPI)-anchored membrane protein frequently over-expressed in human carcinomas and associated with metastasis and poor prognosis. Previous work has shown that CD24 expression affects various cellular properties such as invasion, adhesion, proliferation and apoptosis in vitro as well as tumor growth in vivo. By analyzing underlying mechanisms of CD24-dependent tumor cell behaviour we discovered the influence of CD24 on STAT3 signaling and gene regulation via the tyrosine kinase c-Src. Altered activity of c-Src mediated by CD24 knock-down was responsible for reduced levels of phosphorylated STAT3 (Y705). Diminished activity of STAT3 was confirmed by luciferase-reporter assays. Silencing of c-Src, similar to CD24, reduced the expression of prototype STAT3-regulated genes. Likewise, the over-expression of CD24 augmented c-Src activity, the recruitment of c-Src into lipid rafts, levels of p-STAT3 and the expression of STAT3-dependent target genes. Functionally, depletion of CD24 reduced cell proliferation and increased apoptosis, suggesting a pivotal role of regulated target genes for these functional effects. Even more profoundly, CD24 expression was accompanied with the secretion of the STAT3 target IL-6. We could show a strong correlation between IL-6 secretion and CD24 expression in tumor cell lines. Furthermore, treatment with conditioned cell culture medium from CD24 over-expressing- or CD24 knock-down tumor cells initiated paracrine STAT3 signaling and gene regulation in the monocytic precursor cell line THP-1. This suggested a regulative role of CD24 on the tumor microenvironment. We propose that CD24 is capable of influencing not only tumor cellular properties but also has impact on the cytokine milieu of the tumor microenvironment. Citation Format: Niko P. Bretz, Alexei V. Salnikov, Gerhard Moldenhauer, Peter Altevogt. CD24 affects tumor cell properties and cytokine secretion in a STAT3-dependent fashion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B3.