Increased Levels of Hypoxia-Inducible Factor-1 alpha Are Associated with Bcl-xL Expression, Tumor Apoptosis, and Clinical Outcome in Chondrosarcoma

Hypoxia-inducible factor (HIF)-1 alpha is a key nuclear transcription factor that regulates the cellular response to hypoxia, and is important for solid tumor growth and survival. However; the underlying role of HIF-1 alpha in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF-1 alpha in chondrosarcoma, and its association with clinicopathologic features, Bcl-xL expression, apoptosis index (AI), and overall survival of patients with chondrosarcoma. Our results shown that the protein levels of HIF-1 alpha were increased, and the mRNA and protein levels of Bcl-xL were also increased in SW1353 cells under hypoxic conditions. In eight patients with chondrosarcoma, increased expression of HIF-1 alpha and Bcl-xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20(58.3%) showed high HIF-1 alpha protein expression as compared to benign cartilage tumors. Increased HIF-1 alpha expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF-1 alpha expression was significantly associated with Bcl-xL expression and AI. More significantly, the survival rate of patients with HIF-1 alpha high tumors was significantly lower than that of patients with HIF-1 alpha low tumors. These findings suggest that increased HIF-1 alpha levels mediated up-regulation of Bcl-xL play a prominent role in evasion of apoptosis and tumor progression, and can be predictive for the prognosis in human chondrosarcoma. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 143-151, 2011