Jing Yue, Jin Yue, Wang Yujia, Chen Sheng, Zhang Xiaoxin, Song Yuxian, Wang Zhiyong, Pu Yumei, Ni Yanhong, Hu Qingang
Central Laboratory of Oral Disease, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
J Cell Physiol. 2019 Sep;234(9):15581-15593. doi: 10.1002/jcp.28205. Epub 2019 Jan 31.
Oral squamous cell carcinoma (OSCC) is a highly lethal cancer in the world, and the prognosis of OSCC is poor with a 60% 5-year survival rate in recent decades. Here, we introduced a novel secretory and acid glycoprotein with cysteine rich (secreted protein acidic and rich in cysteine, SPARC), which is correlated with the worst pattern of invasion (WPOI) and prognosis of OSCC. SPARC expression levels were measured in OSCC tissues and normal tissues using quantitative polymerase chain reaction and immunohistochemistry. The influence of SPARC on cell proliferation was examined by cell counting kit-8, colony formation, and Edu tests. Then, the effect of SPARC on the metastasis of OSCC cells was detected by wound healing and transwell migration assays. Next, the biologic characteristics of SPARC shared by STRING were analyzed. Furthermore, the underlying mechanisms were confirmed by western blot analysis. SPARC revealed higher expression in OSCC tissues than nontumor tissues. Higher SPARC expression was correlated with poorer tumor differentiation, poorer WPOI pattern, and significantly and shorter overall survival. Knockdown SPARC significantly restrained OSCC cell growth, migration, and invasion. In addition, bioinformatics analysis found SPARC had a coexpression network with the platelet-derived growth factor-B (PDGFB) and PI3K/AKT signaling pathways with minimal false discovery rate. Furthermore, SPARC promotes OSCC cells metastasis by regulating the expressions of PDGFB, PDGFRβ, p-PDGFRβ , and the PI3K/AKT pathway. Higher SPARC expression was positively correlated with poor WPOI and differentiation in OSCC. SPARC activates the PI3K/AKT/PDGFB/PDGFRβ axis to promote proliferation and metastasis by OSCC cell lines. Therefore, SPARC may be a potential therapeutic target for patients with OSCC.
口腔鳞状细胞癌（OSCC）是一种在全球具有高度致死性的癌症，近几十年来，OSCC的预后较差，5年生存率为60%。在此，我们引入了一种新型的富含半胱氨酸的分泌性酸性糖蛋白（分泌性富含半胱氨酸的酸性蛋白，SPARC），它与OSCC的最差侵袭模式（WPOI）和预后相关。使用定量聚合酶链反应和免疫组织化学方法检测OSCC组织和正常组织中SPARC的表达水平。通过细胞计数试剂盒-8、集落形成和Edu试验检测SPARC对细胞增殖的影响。然后，通过伤口愈合和Transwell迁移试验检测SPARC对OSCC细胞转移的作用。接下来，分析STRING共享的SPARC的生物学特性。此外，通过蛋白质印迹分析证实潜在机制。SPARC在OSCC组织中的表达高于非肿瘤组织。较高的SPARC表达与较差的肿瘤分化、较差的WPOI模式以及显著缩短的总生存期相关。敲低SPARC可显著抑制OSCC细胞的生长、迁移和侵袭。此外，生物信息学分析发现SPARC与血小板衍生生长因子-B（PDGFB）和PI3K/AKT信号通路存在共表达网络，假发现率极低。此外，SPARC通过调节PDGFB、PDGFRβ、p-PDGFRβ的表达以及PI3K/AKT途径促进OSCC细胞转移。在OSCC中，较高的SPARC表达与不良的WPOI和分化呈正相关。SPARC激活PI3K/AKT/PDGFB/PDGFRβ轴以促进OSCC细胞系的增殖和转移。因此，SPARC可能是OSCC患者的潜在治疗靶点。
