Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, NO. 22, Zhongguancun South Street, Haidian District, Beijing, 100081, China.
Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
BMC Cancer. 2021 Dec 1;21(1):1283. doi: 10.1186/s12885-021-09025-7.
Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway.
CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo.
Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin.
IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.
癌症干细胞（CSCs）驱动肿瘤的发生和进展，并参与肿瘤的化疗耐药性。我们最近发现，高表达 CD10 的口腔鳞状细胞癌（OSCC）细胞（CD10H 细胞）表现出与癌症干细胞（CSC）相关的特征，这些特征反过来又影响肿瘤的生长、上皮-间充质转化（EMT）和对顺铂的耐药性。在这项研究中，我们在体外和体内进一步研究了这一机制。我们假设，IL8 可能通过 ERK 通路调节 CD10 阳性口腔癌细胞的迁移、侵袭和对顺铂的耐药性。
使用 CD10 MicroBead Kit 选择高表达和低表达 CD10 的 HN6 细胞。通过蛋白质芯片检测筛选靶蛋白 IL8。应用慢病毒转导和特异性抑制剂来研究信号通路。实时 PCR、Western blot 和免疫组化用于分析 mRNA 和蛋白表达；Transwell assay、球体形成 assay 和细胞活力 assay 用于研究体外细胞生物学行为；异种移植动物模型用于评估体内肿瘤形成率。
CD10 的过表达促进了 CSC 相关基因的表达，并增强了 HN6 细胞的迁移、侵袭、球体形成和化疗耐药性。此外，在 OSCC 肿瘤组织和高表达 CD10 的细胞系（HN6 和 CAL27）中检测到 IL8 的过表达。CD10H HN6 细胞分泌的 IL8 通过 p-ERK 信号通路促进迁移和侵袭，并恢复肿瘤对顺铂的敏感性，而抑制 IL8 则增加了对顺铂的化疗敏感性。
CD10 阳性细胞分泌的 IL8 通过 p-ERK 信号通路促进 OSCC 的迁移、侵袭和顺铂耐药性。
