人原发性小肠恶性黑色素瘤裸鼠肺转移模型的建立

目的 建立原发性小肠恶性黑色素瘤肺转移动物模型.方法 采用人原发性小肠恶性黑色素瘤肺转移瘤的新鲜瘤组织块植入裸鼠小肠黏膜层内,当裸鼠体内形成肺转移瘤后重复筛选4次,再将肺转移瘤植入另一只裸鼠小肠黏膜行鼠问连续传代.观察原位移植成瘤率和转移率,进行形态学、染色体核型和流式细胞仪分析.结果 建成的人原发性小肠恶性黑色素瘤裸鼠肺转移模型命名为HSIM-0601,瘤细胞胞质内可见大量黑色素颗粒及黑色素复合体,S-100、HMB-45呈阳性表达.染色体数57～59条;流式细胞DNA指数值1.49,均为异倍体.HSIM-0601已传至26代,共移植裸鼠173只,成瘤率和液氮冻存复苏成活率均为100%.肺转移率为100%(173/173),淋巴结转移率为61.3%(106/173).结论 首次成功地建立了人原发性小肠恶性黑色素瘤裸鼠原位移植肺转移模型HSIM-0601.完整地模拟了人小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤肺转移机制和抗转移治疗提供了理想的动物模型.

Establishment of lung metastasis model of human primary malignant melanoma in the small intestine in nude mice

Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and HMB-45 were positive.The number of chromosome was between 57 and 59.DNA index was 1.49.HSIM-0601 was passed for 26 generations.A total of 173 nude mice were used for tumor transplantation.The growth rate of the transplanted tumors and resuscitation rate of liquid nitrogen cryopreservation were both 100%.In HSIM-0601.lung metastasis rate was 100%(173/173)and lymph node metastasis rate was 61.3%(106/173).Conclusions The HSIM-0601 successfully mimics the natural clinicopathologic course of patients with primary small intestinal melanoma,and provides an ideal animal model for research on pathogenesis,metastasis and experimentM therapy of malignant lymphoma in the small intestine.