Hüsemann Yves, Geigl Jochen B, Schubert Falk, Musiani Piero, Meyer Manfred, Burghart Elke, Forni Guido, Eils Roland, Fehm Tanja, Riethmüller Gert, Klein Christoph A
Department of Pathology, Division of Oncogenomics, University of Regensburg, Regensburg 93053, Germany.
Cancer Cell. 2008 Jan;13(1):58-68. doi: 10.1016/j.ccr.2007.12.003.
It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2 transgenic glands displayed disseminated tumor cells and micrometastasis in bone marrow and lungs. The number of disseminated cancer cells and their karyotypic abnormalities were similar for small and large tumors in patients and mouse models. When activated by bone marrow transplantation into wild-type recipients, 80 early-disseminated cancer cells sufficed to induce lethal carcinosis. Therefore, release from dormancy of early-disseminated cancer cells may frequently account for metachronous metastasis.
人们普遍认为转移是癌症进展中的晚期事件。然而，我们在此表明，肿瘤细胞可从HER-2和PyMT转基因小鼠最早的上皮改变以及女性原位导管癌中发生全身播散。移植单个癌前HER-2转基因腺体的野生型小鼠在骨髓和肺中出现了播散的肿瘤细胞和微转移。患者和小鼠模型中，大小肿瘤的播散癌细胞数量及其核型异常情况相似。当通过骨髓移植激活并植入野生型受体时，80个早期播散的癌细胞足以诱发致命的癌转移。因此，早期播散癌细胞从休眠状态中释放可能常常是异时转移的原因。
