Abstract 417: Tax-interacting protein 1 (TIP-1) as one biomarker of invasive astrocytomas

Abstract

Abstract Despite the comparatively low incidence of astrocytomas to other human cancers, mortality rates of cancer patients with invasive astrocytomas are extremely high. Despite decades of therapeutic research, curative intervention is still nonexistent for high grade astrocytomas; patient care ultimately focuses on palliative management. Even with aggressive surgical, radio- and chemo- therapies, highly invasive astrocytomas have poor prognosis with an average survival time of 12 months. We intend to identify and characterize new biomarkers or molecular targets for effective diagnostics or therapeutics development. In our previous study of recombinant peptide for tumor imaging, we found that tumor xenografts formed with D54 glioma cells had relatively higher binding to HVGGSSV peptide than other tumor models. It was further elucidated that Tax-interacting protein 1 (TIP-1) contributes to the HVGGSSV peptide binding within tumors. Immunohistochemistry study of human brain tissues revealed significantly elevated expression of TIP-1 within astrocytomas, while compared to normal brain tissue or oligodendrogliomas that showed faint to negative staining of TIP-1. More interestingly, the highest expression of TIP-1 was found in glioblastoma multiforme, the highly invasive astrocytomas. To elucidate biological relevance of TIP-1 expression in invasive astrocytomas, human glioma cell line D54 was genetically engineered to have elevated or down-regulated expression of TIP-1. Tumorigenesis studies indicated that TIP-1 positively regulated tumor formation in nude mice. Knocking-down TIP-1 within D54 cells resulted in delayed tumor formation and decreased tumor growth rate. However, over-expression of TIP-1 within D54 cells lead to fast growing tumors in vivo, histological examination showed the TIP-1 over-expressing D54 tumors were sporadic with presence of necrotizing tissues surrounded by anaplatic cells, one characteristic of glioblastomas multiforme. In vitro characterization further demonstrated that the TIP-1 over-expressing cells had improved invasion capability, TIP-1 is dominantly expressed in invasion front of D54 cells. Biochemical studies indicated that the TIP-1 modulates cytoskeleton organization by interacting with multiple proteins. In summary, this study demonstrated that TIP-1 is one biomarker of invasive astrocytomas, and might be one potent molecular target for therapeutics development. 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 417.