Monitoring serial changes in circulating human breast cancer cells in murine xenograft models
Monitoring serial changes in circulating human breast cancer cells in murine xenograft models
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DOI：
10.1158/0008-5472.can-08-0630
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发表时间：
2008-07-15
期刊：
影响因子：
11.2
通讯作者：
Luker, Gary D.
中科院分区：
文献类型：
--
作者：
Eliane, Jean-Pierre;Repollet, Madeline;Luker, Gary D.
循环肿瘤细胞(CTC)在包括乳腺癌、结肠癌和前列腺癌在内的几种癌症中是一种强大的预后和预测生物标志物。CTC在肿瘤转移中的研究以及作为癌症生物标志物的进一步发展一直受到无法在小鼠癌症模型中重复监测CTC的限制。我们已经验证了一种从活体小鼠的血液样本中计数CTC的方法，该方法使用了一种用于定量患者CTC的体外诊断系统的改进版本。对不同的采血途径进行了试验，以确定一种在不污染正常小鼠上皮细胞的情况下从荷瘤小鼠身上重复回收CTC的方法。CTC存在于携带几种不同乳腺癌细胞系原位异种移植的小鼠的血液样本中，以及来自患者活检组织的原代乳腺癌细胞。我们还表明，该技术可用于连续监测小鼠人乳腺癌异种移植模型中的CTC。这些结果为研究CTC在小鼠上皮癌模型中的作用建立了新的方法，为研究CTC在肿瘤中的分子调控以及作为治疗效果的生物标志物奠定了基础。
Circulating tumor cells (CTC) are emerging as a powerful prognostic and predictive biomarker in several types of cancer, including breast, colon, and prostate. Studies of CTC in metastasis and further development of CTC as a biomarker in cancer have been limited by the inability to repetitively monitor CTC in mouse models of cancer. We have validated a method to enumerate CTC in blood samples obtained from living mice using a modified version of an in vitro diagnostic system for quantifying CTC in patients. Different routes of blood collection were tested to identify a method to reproducibly recover CTC from tumor-bearing mice without interference from contaminating normal murine epithelial cells. CTC are present in blood samples from mice bearing orthotopic xenografts of several different breast cancer cell lines and primary breast cancer cells from patient biopsies. We also show that this technology can be used for serial monitoring of CTC in mouse xenograft models of human breast cancer. These results establish a new method for studying CTC in mouse models of epithelial cancer, providing the foundation for studies of molecular regulation of CTC in cancer and CTC as biomarker for therapeutic efficacy.