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作 者:苏广彦[1] 刘玉琴[1] 任乐荣[1] 刘险峰[1] 顾蓓[1] 董继红[1] 高进[1]
机构地区:[1]中国医学科学院基础医学研究所北京协和医学院基础医学院,北京100005
出 处:《中华病理学杂志》2007年第11期760-763,共4页Chinese Journal of Pathology
基 金:国家973重点基础研究发展规划基金(2002CB513100-2);科技部自然科技资源平台基金资助项目(2005DKA21502)
摘 要:目的模拟乳腺癌患者术后体内有少量肿瘤细胞存在,但长期无症状,也无特殊体征的特点而建立小鼠乳腺癌休眠模型并确定休眠细胞的存在。方法采用500个小鼠乳腺癌 Ca761-03细胞肌肉接种于30只615小鼠,以小鼠2个月(相当人5年)不成瘤为休眠标准,按休眠观察组、休眠验证组和复发验证组三组(各10只小鼠)连续观察肿瘤休眠发生情况。肿瘤细胞休眠的确认方法为,采用给予连续外伤刺激,接种部位取材,组织固定和 HE 染色观察肿瘤再生成情况。结果 500个小鼠乳腺癌 Ca761-03细胞肌肉接种于小鼠2个月后,有30%小鼠成瘤,70%处于休眠状态。休眠肿瘤给予连续外伤刺激5个月后,有90%小鼠成瘤。显示乳腺癌肿瘤细胞可以在小鼠体内长期保持休眠状态,在外伤刺激的作用下,休眠的肿瘤细胞可以再次增殖,成为肿瘤复发的根源。结论成功建立了小鼠乳腺癌休眠模型,并用外伤刺激休眠细胞增殖的方法确定了休眠肿瘤细胞在体内的存在。这一动物模型填补了实体瘤休眠动物模型缺乏的空白。Objective Tumor dormancy has been defined clinically as a condition in which tumor cells are present but do not grow for a long period of time. Breast cancer is noted for its long periods of tumor dormancy and metastases can occur many years after treatment. Method Simulating the characteristics of breast cancer patients after treatment, we established the animal model of breast cancer dormancy by inoculating 500 Ca761-03 cells into the limb muscle of 615 mice and then selecting animals with tumor dormancy 2 months post inoculation ( corresponding to 5 years for humans ). Results Two months after inoculation of Ca761-03 cells into the muscle of 615 mice, tumor occurred in 30% of the mice. The remaining 70% of mice did not show tumor growth. After repeated traumatic stimulation, 90% of the mice developed tumors after 5 months, therefore representing tumor dormancy. Condusions These results demonstrate that breast cancer cells can remain in a dormant state for long periods of time in vivo. Trauma can stimulate the dormant tumor cells to proliferate again, and causes tumor relapse. This murine model system promises a sound animal model for the study of solid tumor dormancy.
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