Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Oral pathology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Oral Dis. 2020 Apr;26(3):547-557. doi: 10.1111/odi.13279. Epub 2020 Jan 29.
CD44, a cell-surface glycoprotein, functions as a receptor for hyaluronic acid. Our research group has previously shown that CD44 is a biomarker for the CD44 cells (tumor-initiating cells; TICs) in murine salivary gland tumors. However, little is known concerning the biological roles of CD44 in the tumorigenesis of pleomorphic adenoma. The present study is aimed to investigate the effects of CD44 on the proliferation, invasive capability, and apoptosis of TICs in vitro, as well as the tumorigenicity of TICs in vivo. The results demonstrated that knockdown of CD44 attenuated the malignant phenotype of TICs. Furthermore, in vivo xenograft studies indicated that CD44 knockdown inhibited tumorigenesis of pleomorphic adenoma. In addition, neither the CD44 cells nor the CD44-modified CD44 cells developed neo-tumors, which indicated that overexpression of CD44 did not enable the CD44 cells to be transformed into TICs. Taken together, these data demonstrate that CD44 not only acts as a biomarker, but also functions as a key player in the tumor-initiating capacity of TICs. These results shed light on the pathogenesis of salivary gland tumors and provide a potential therapeutic target for treating pleomorphic adenoma.
CD44 是一种细胞表面糖蛋白，作为透明质酸的受体发挥作用。我们的研究小组先前表明，CD44 是小鼠唾液腺肿瘤中 CD44 细胞（肿瘤起始细胞；TICs）的生物标志物。然而，关于 CD44 在多形性腺瘤发生中的生物学作用知之甚少。本研究旨在探讨 CD44 对 TICs 体外增殖、侵袭能力和凋亡的影响，以及 TICs 体内致瘤性的影响。结果表明，CD44 敲低减弱了 TICs 的恶性表型。此外，体内异种移植研究表明，CD44 敲低抑制了多形性腺瘤的发生。此外，CD44 细胞和 CD44 修饰的 CD44 细胞均未形成新肿瘤，这表明 CD44 的过表达并未使 CD44 细胞转化为 TICs。总之，这些数据表明 CD44 不仅作为一种生物标志物，而且作为 TIC 起始能力的关键参与者发挥作用。这些结果阐明了唾液腺肿瘤的发病机制，并为治疗多形性腺瘤提供了一个潜在的治疗靶点。
