Raw Data for the article: High-Resolution Secretome Analysis of Chemical Hypoxia Treated Cells Identifies Putative Biomarkers of Chondrosarcoma

Chondrosarcoma is the second most common bone tumor, accounting for 20% of all cases. Little is known about the pathology and molecular mechanisms involved in the development and in the metastatic process of chondrosarcoma. As a consequence, there are no approved therapies for this tumor and surgical resection is the only treatment currently available. Moreover, there are no available biomarkers for this type of tumor, and chondrosarcoma classification relies on operator-dependent histopathological assessment. Reliable biomarkers of chondrosarcoma are urgently needed, as well as greater understanding of the molecular mechanisms of its development for translational purposes. Hypoxia is a central feature of chondrosarcoma progression. The hypoxic tumor microenvironment of chondrosarcoma triggers a number of cellular events, culminating in increased invasiveness and migratory capability. Herein, we analyzed the effects of chemically-induced hypoxia on the secretome of SW 1353, a human chondrosarcoma cell line, using high-resolution quantitative proteomics. We found that hypoxia induced unconventional protein secretion and the release of proteins associated to exosomes. Among these proteins, which may be used to monitor chondrosarcoma development, we validated the increased secretion in response to hypoxia of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme well-known for its different functional roles in a wide range of tumors. In conclusion, by analyzing the changes induced by hypoxia in the secretome of chondrosarcoma cells, we identified molecular mechanisms that can play a role in chondrosarcoma progression and pinpointed proteins, including GAPDH, that may be developed as potential biomarkers for the diagnosis and therapeutic management of chondrosarcoma.软骨肉瘤（Chondrosarcoma）是第二大常见骨肿瘤，约占所有骨肿瘤病例的20%。目前学界对软骨肉瘤发生发展及转移过程中的病理特征与分子机制仍知之甚少。因此，目前尚无获批的软骨肉瘤靶向治疗方案，手术切除仍是唯一可选的治疗手段。此外，该类肿瘤暂无可用的生物标志物，软骨肉瘤的分型仍依赖于操作者主观判断的组织病理学评估。学界亟需可靠的软骨肉瘤生物标志物，并为转化医学研究深入解析其发生发展的分子机制。缺氧是软骨肉瘤进展的核心特征，软骨肉瘤的缺氧肿瘤微环境可引发一系列细胞事件，最终导致肿瘤侵袭与迁移能力增强。本研究采用高分辨率定量蛋白质组学技术，分析了化学诱导缺氧对人软骨肉瘤细胞系SW 1353分泌组的影响。研究发现，缺氧可诱导非经典蛋白质分泌，并促进与外泌体（exosomes）相关的蛋白质释放。在这些可用于监测软骨肉瘤发生发展的蛋白质中，我们验证了缺氧刺激下甘油醛-3-磷酸脱氢酶（glyceraldehyde 3-phosphate dehydrogenase, GAPDH）的分泌水平显著升高——该糖酵解酶因在多种肿瘤中发挥多种不同功能而被广泛研究。综上，本研究通过分析缺氧诱导的软骨肉瘤细胞分泌组变化，阐明了可能参与软骨肉瘤进展的分子机制，并筛选出包括GAPDH在内的潜在蛋白质标志物，有望用于软骨肉瘤的诊断与临床治疗管理。