The Anti-Apoptotic Protein Lifeguard Is Expressed in Osteosarcoma, Chondrosarcoma, and Soft Tissue Sarcoma

抗凋亡蛋白 Lifeguard 在骨肉瘤、软骨肉瘤和软组织肉瘤中表达

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Abstract

INTRODUCTION: The success of modern chemotherapy in overall survival of patients with advanced stages of osteosarcoma and soft tissue sarcoma has reached a plateau. Therefore, a deeper understanding of molecular mechanisms behind deregulated apoptosis in sarcoma is essential for the cure of patients with advanced stages of osteosarcoma and soft tissue sarcoma. Lifeguard (LFG) is a member of the Bax inhibitor-1 (BI-1) protein family and has anti-apoptotic effects by inhibiting Fas-mediated cell death signaling. Although LFG has been proven to be expressed in several breast cancer tissues, the expression and function of LFG regarding apoptosis in different subtypes of sarcoma remains unclear. METHODS: In the present study, the expression of LFG in osteosarcoma (50 samples), chondrosarcoma (28 samples), and soft tissue sarcoma (total 55 samples) with different tumor stages for each sarcoma subtype was analyzed. For each subtype, clinical TNM classification (tumor, node, metastasis) and pathological grading were determined and compared to healthy tissues. Soft tissue sarcoma subtypes included liposarcoma, dermatofibrosarcoma, angiosarcoma, leiomyosarcoma, malignant schwannoma, and synovial cell sarcoma. RESULTS: In this study, significantly higher expressions of anti-apoptotic LFG protein in osteosarcoma, chondrosarcoma, and many different subtypes of soft tissue sarcoma were found, compared to healthy tissues. More importantly, a positive correlation between LFG expression and tumor stage for osteosarcoma was found. CONCLUSION: LFG protein might play an important role in inhibition of Fas-mediated apoptosis in osteosarcoma cells, with possible potential for targeted tumor therapy in osteosarcoma.

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