人源食管鳞状细胞癌移植瘤模型的建立及其增殖信号通路特征

目的:构建人食管鳞状细胞癌组织来源的移植瘤模型,并了解其病理学特征和增殖相关的信号通路活化情况。方法:将人食管癌组织移植于重度联合免疫缺陷(SCID)小鼠皮下,待移植瘤长成后对其进行鼠间连续传代。观察第1、第2、第3代移植瘤的生长特性。并对患者肿瘤组织、第1代和第3代移植瘤进行HE染色和CK5/6、p63、p40免疫组织化学染色分析。Western blot实验检测4例所建立的移植瘤中m TOR、p-m TOR、p70S6K、pp70S6K、Akt1、p-Akt(Ser473)、Erk1/2和p-Erk1/2的表达情况。结果:成功建立移植瘤模型,移植瘤生长稳定并能连续传代。各移植瘤组织病理组织类型和CK5/6、p63、p40表达阳性与患者肿瘤组织一致。而在不同病人来源的移植瘤组织中信号转导通路蛋白的活化程度差异有统计学意义。结论:成功建立了人食管鳞状细胞癌组织来源的食管癌移植瘤模型,初步论证该模型能够反映患者的病理特征。

Establishment of patient-derived esophageal squamous-cell carcinoma xenograft in mice and characteristics of signaling pathways related to proliferation in SCID mice

AIM: To establish and characterize the patient-derived esophageal squamous-cell carcinoma xenograft (PDECX) in mice. METHODS: The samples of human esophageal cancer were grafted into severe combined immunodeficient (SCID) mice. The xenografts were transferred to SCID mice when the first passage of xenografts grew up. The growth of tumors in the first, second and third passages was observed. HE staining was performed. The expression of CK5/6, p63 and p40 in the patient samples, and the first and third passages of the xenografts were detected by immunohistochemical analysis. The expression of mTOR, p-mTOR, p70S6K, p-p70S6K, Akt1, p-Akt (Ser473), Erk1/2 and p-Erk1/2 were determined by Western blot.RESULTS: The PDECX was successfully established. The positive expression of CK5/6, p63 and p40 in the xenografts was consistent with that in the patients' samples. The levels of phosphorylated and total proteins of proliferation-related signaling pathways were different in the xenografts from different patients.CONCLUSION: The PDECX model adequately reflects the tumal heterogeneity that is observed in the patients.