Abstract 5090: The role of p32 in brain metastasis

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Abstract Brain metastases are among the most feared complication in cancer. To develop effective and targeted therapies for treatment of brain metastases, we need a better understanding of the mechanisms that control cancer cell growth within the brain microenvironment. We previously found evidence that brain metastatic cells have increased rates of oxidative phosphorylation and redox potential compared to tumor cells from extracranial lesions. Here we sought to identify mechanisms involved, and to identify potential targets for the inhibition of metastatic growth in the brain. Many of the genes involved in transformation such as Myc, AKT, and p53 have extensive effects on the metabolism, suggesting that tumors might be susceptible to antimetabolic drugs. One of the proteins that has been shown to be upregulated in many solid tumors is the protein p32. P32 is a multi-compartmental and multi-functional protein which has a regulatory function in oxidative phosphorylation, in addition to being involved in the regulation of apoptosis and autophagy. We found p32 expressed in human cancer cells capable of seeding brain metastases in immune deficient mice, and we hypothesized that p32 contributes to cell survival and proliferation within the brain microenvironment. We knocked down p32 in brain homing variants of the MDA-MB-231 and MDA-MB-435 metastasis cell models. Following luciferase tagged tumor cells by non-invasive bioluminescence imaging revealed that stable p32 knockdown greatly reduced metastatic activity in both MDA-MB-231 brain specific variant and the MDA-MB 435 cell line. Furthermore, our genomic profiling of p32 knock-down and control cells identified candidate genes in the respiration chain involved in p32-dependent tumor cell survival and growth that may impact progression to brain metastasis. Thus, the expression and functionality of p32 in tumor cells capable of colonizing the brain appears associated with changes in crucial pathways that enable the tumor cells to proliferate and survive within the brain microenvironment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5090.