口腔鳞癌中CD24的表达、作用和治疗靶点价值

目的：明确口腔鳞癌组织和细胞中黏液素样细胞表面黏附分子CD24的表达模式、作用及其作为治疗靶点的潜在价值。方法：利用免疫组化、real-time RT-PCR和Western blot方法，明确CD24在78例人口腔组织标本和59例动物模型金地鼠（Hamster buccal）颊囊组织标本，以及口腔癌前病变上皮细胞DOK4、口腔鳞癌细胞CAL-27和WSU-HN6中的表达模式；以CAL-27和WSU-HN6细胞为模型，明确在常规和无血清成球培养条件下，全反式维甲酸（all-trans retinoic acid, ATRA）和CD24抗体对CAL-27和WSU-HN6细胞及肿瘤球生长的影响，并观察它们是否影响这两种细胞中CD24的表达。结果：人和金地鼠组织的免疫组织染色结果显示，在正常/单纯增生组织、轻度/中度异常增生组织、重度异常增生和鳞癌组织中均依次呈现CD24表达递增的现象(P＜0.05)；与DOK细胞相比较，CAL-27和WSU-HN6口腔鳞癌细胞中CD24表达上调(P＜0.05)。相对于癌前病变细胞DOK，口腔鳞癌细胞CAL-27和WSU-HN6具有更强的增殖和肿瘤球成球的潜能(P＜0.05)。ATRA能够有效地抑制这两种口腔鳞癌细胞的CD24表达、体外增殖和肿瘤球形成的能力(P＜0.05)，而CD24抗体虽然也一样能够抑制口腔鳞癌细胞的增殖和肿瘤球形成(P＜0.05)，但却不影响其CD24的表达。结论：CD24在口腔鳞癌中表达上调，具有促进口腔鳞癌细胞增殖和肿瘤球形成的作用，维甲酸和CD24抗体皆能以CD24为靶点有效地抑制口腔鳞癌细胞的增殖和肿瘤球形成。

Expression,roles and therapy target values of CD24 in oral squamous cell carcinoma

Objective:To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy.Me-thods:Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues.Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells,oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA)and CD24 antibody on CD24 expression,and the proliferation and tumorsphere formation capacity of these two cell lines.Results:CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05),as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05).CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05 ).Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05).Among them ATRA at least involved partially in the proliferation by down-regulating the CD24 expression (P<0.05 ),while CD24 antibody blocking had no effect on the CD24 expression.Conclusion:CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells.Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target.