Abstract 3956: Combination of SPARC and radiation suppresses HSP27 and induces p21(CIP1/WAF1) in neuroblastoma tumor cells

Neuroblastoma (NBL) is the third most common malignancy in children and accounts for more than 15% of cancer-related deaths in children in the US. Approximately 50% of patients present with advanced-stage and/or high risk disease. Despite significant intensification of conventional chemotherapy regimens, the long-term survival rates for these children remain less than 40%. A somewhat improved outcome has been obtained with multimodality therapeutic approaches including chemotherapy, surgery, autologous bone marrow transplantation, radiation therapy and use of biological agents. However, long-term survival rates for children with high-risk disease remain poor and survivors experience significant immediate and late toxicities which further limits conventional chemotherapy dose intensification. Novel biological therapies are therefore much needed. Secreted protein, acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, belongs to the matricellular family of secreted proteins, which also includes thrombospondin 1 and 2, osteopontin, and tenascins C and X. The biological functions of SPARC are known to be variable in human cancers. In neuroblastoma however, SPARC expression has been found to be associated with impaired tumor growth and angiogenesis. Our previous studies showed that overexpression of SPARC induced autophagy-mediated apoptosis in neuroblastoma cells. In the present study we have attempted to decipher the mechanisms of this apoptotic induction. We u...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research