Abstract 5138: The regulation of CD44 expression in malignant brain tumor cells

Abstract

Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain tumor that demonstrates a high growth rate and the capacity to invade surrounding brain tissue. These characteristics result in a dismal prognosis for GBM patients. Current treatment options for GBM tumors involve surgical resection followed by radiation and/or chemotherapy. Disappointingly, GBM tumors are or become resistant to radiation and chemotherapy, and the invasiveness of GBM precludes curative removal of the tumor. GBM cells infiltration has been associated with the transmembrane glycoprotein, CD44, which is the principle cell surface receptor for hyaluronic acid (HA). The molecular mechanisms that regulate CD44 in GBM are not fully understood. However, CD44 protein expression has been associated with an AP-1 transcription factor, fos related antigen 1 (Fra-1), in another aggressive cancer, mesothelioma. Therefore, we investigated the regulation of CD44 expression in human glioma cells by Fra-1. Human GBM cell lines, U-251 MG, U-1242 MG, and A-172, were exposed to either epidermal growth factor (EGF, 20 ng/ml) or hepatocyte growth factor (HGF, 50 ng/ml) at varying time points and Western blot analysis was used to determine the protein expression of CD44 and Fra-1. CD44 and Fra-1 expression levels increased with longer exposures (4 to 24 hr) to EGF and HGF. To determine whether Fra-1 takes part in the regulation of CD44 expression, we utilized transient gene knockdown using siRNA directed against fra-1. fra-1-siRNA decreased Fra-1 expression in EGF- and HGF-treated GBM cells. Following EGF stimulation and fra-1-siRNA treatments, CD44 expression also decreased. However, HGF stimulation of fra-1-siRNA treated GBM cells showed no change in CD44 expression. These data suggest that Fra-1 regulation of CD44 expression is growth factor-specific. To investigate whether CD44-mediated cell adhesion is promoted by the expression of Fra-1, we analyzed GBM cell adhesion to HA. U-251 MG and U-1242 MG cell lines demonstrated an increase adherence to HA after growth factor simulation, 4hr and 24 hr respectively. This data is comparable to the initial western blot analysis of the GBM cells after growth factor simulation. However, A-172 cells did not adhere to HA regardless of growth factor stimulation. These data suggest that CD44 binding to HA is cell line specific. Taken together, our results suggest that CD44-mediated HA binding of GBM cells can be regulated by Fra-1 expression. 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 5138.