Expression of the Inflammatory Molecule HMGB1 in Human Osteosarcoma and its Clinical Relevance

Abstract

High mobility group box 1 (HMGB1), known as a pro-inflammatory cytokine and chromatin-binding molecule, plays an important role in the carcinogenesis and metastasis of various tumors. The present study aimed to investigate the expression of HMGB1 in human osteosarcoma and its clinical relevance. At first, human osteosarcom tissues and their corresponding adjacent non-cancerous tissues (ANCT) from forty consecutive cases were collected. The expression of HMGB1 was detected by immunohistochemical assay through tissue microarray procedure and the correlation of HMGB1 expression with clinicopathologic factors was evaluated. Secondly, through small hairpin RNA(shRNA)-mediated HMGB1 knockdown in MG-63 osteosarcoma cells, we observed the changes of the biological behaviors of the osteosarcoma cells. As a consequence, the rate of positive expression of HMGB1 was significantly higher in osteosarcoma tissues than in the ANCT (60% vs 15%, P < 0.01). HMGB1 expression had significant positive correlation with Ennecking staging ( P = 0.034) and distant metastases ( P = 0.003), but had no correlation with the factors including age and gender of the patients, or histology and location of the tumor (each P > 0.05). Knockdown of HMGB1 down-regulated the expression of p-AKT, p-PI3K, PCNA, MMP-9 and CyclinD1, while it up-regulated the expression of cleaved caspase-3. More importantly, HMGB1 knockdown inhibited the proliferative activities and invasive potential, and induced apoptosis and cycle arrest in MG63 osteosarcoma cells. Taken together, our results indicate that HMGB1 was highly expressed in human osteosarcoma tissues, and the patients with higher HMGB1 expression in osteosarcoma tissues were more likely to have progression and metastasis of the disease. Knockdown of HMGB1 could inhibit the proliferation and invasion of osteosarcoma cells and induce its apoptosis through down-regulation of PI3K/AKT signaling pathway. HMGB1 could be a potential therapeutic target for osteosarcoma.