Increased levels of hypoxia‐inducible factor‐1α are associated with Bcl‐xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma

Abstract

Hypoxia-inducible factor (HIF)-1␣ 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␣ in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF-1␣ 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␣ 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␣ and Bcl-xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20 (58.8%) showed high HIF-1␣ protein expression as compared to benign cartilage tumors. Increased HIF-1␣ expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF-1␣ expression was significantly associated with Bcl-xL expression and AI. More significantly, the survival rate of patients with HIF-1␣ high tumors was significantly lower than that of patients with HIF-1␣ low tumors. These findings suggest that increased HIF-1␣ 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.

Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

“…Routinely fixed paraffin-embedded tumor specimens were obtained from the department of pathology, Peking University Third Hospital and Tianjin Hospital. Histological grading and surgical staging system of the Musculoskeletal Tumor Society (MSTS) were carefully evaluated as reported previously [28], [29]. The time of follow-up was calculated from the date of surgical operation.…”

“…Protein extraction and Western blot were performed as previously described [28]. Primary antibodies were as follows: anti-actin mouse monoclonal antibody (1∶1000; Sigma), anti-Dkk-1 rabbit monoclonal antibody (1∶1000; Abcam), and anti-β-catenin mouse monoclonal antibody (1∶1000; Transduction Laboratories).…”

“…Accumulated observations have implied that cytoplasmic and/or nuclear β-catenin accumulation is detected in many solid tumors and can be predictive for poor prognosis including sarcoma [21], [25]–[27]. We have previously documented that HIF-1α and HIF-2α play central roles in the pathogenesis of chondrosarcoma, and can be predictive for the prognosis of chondroarcoma patients [28], [29]. More importantly, HIF-1α can trigger nuclear translocation of β-catenin in hypoxia [30].…”

Millimeter wave radiation induces apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 human chondrosarcoma cells

“…Apoptosis disturb regulation of this vital process representing a major causative factor in the pathogenesis of various types of cancers. Apoptosis is characterized by a number of cytological alterations, such as DNA fragmentation, chromatin condensation and activation of cysteinyl aspartate-specific proteinases -the caspases (10,11). The pathways leading to apoptosis may be dependent on or independent of caspases, caspase-dependent apoptosis is a widely recognized phenomenon.…”

Multiple Roles of Angiopoietin-Like 4 in Osteolytic Disease

“…Osteosarcoma, Ewing’s sarcoma, and chondrosarcoma are the most common primary bone tumours, and HIF promotes disease progression in each (75–78), as well as in giant cell tumour of bone (GCTB) (79) and multiple myeloma (80). We detected ANGPTL4 expression in osteoclasts and mononuclear cells present in GCTB (17).…”