Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers.
Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers.
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DOI：
10.1186/bcr3102
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发表时间：
2012-01-25
期刊：
影响因子：
--
通讯作者：
Gong J
中科院分区：
文献类型：
--
作者：
Weng D;Penzner JH;Song B;Koido S;Calderwood SK;Gong J
目前尚不确定转移主要是肿瘤进展的早期还是晚期事件。因此，早期转移和负责传播的细胞的检测可能具有重要的临床意义。使用集落形成试验，研究了携带多瘤病毒中 T 癌基因 (PyMT) 的小鼠在乳腺肿瘤发生的不同阶段的肺部播散和/或转移。免疫细胞化学或免疫组织化学染色用于鉴定负责肺播散和转移的细胞亚群。组织学检查用于显示原发性和转移性肿瘤。在乳腺脂肪垫注射了这些细胞的同基因野生型（WT）小鼠中评估了表达干细胞标记物的细胞的肿瘤起始和转移能力。在携带 PyMT 癌基因的小鼠（MMT 小鼠）的肺部检测到转移性乳腺上皮细胞。这些细胞在乳腺肿瘤发生的早期就被观察到，当时乳腺树通过组织学检查显示为正常（或处于癌前阶段），这表明甚至在完全恶性转化之前就具有播散和转移能力。一些播散细胞和肺转移瘤显示出表面干细胞标记。这些发现表明，来自明显癌前原发病变的干细胞可能是转移的来源。事实上，将 MMT 小鼠的肺组织细胞注射到同基因 WT 小鼠中会导致乳腺肿瘤的形成。这些肿瘤类似于 MMT 供体中的母体乳腺肿瘤以及源自乳腺肿瘤细胞的移植肿瘤。此外，当我们将 GFP MMT 小鼠的肺组织细胞注射到受体 WT 小鼠的脂肪垫中时，在受体 WT 小鼠的肺、淋巴结和血液中检测到播散或转移的 GFP 表达细胞。我们最终确定了表达 CD44 和 Sca1 的乳腺上皮/肿瘤细胞亚群，它们在 MMT 小鼠中主要负责传播和转移。 MMT小鼠乳腺上皮/肿瘤细胞亚群的致瘤和转移潜力在乳腺肿瘤中相对较早地被赋予，这表明癌症干细胞亚群在转移中的潜在作用。
It is still uncertain whether metastasis is predominantly an early or late event in tumor progression. The detection of early metastases and cells responsible for the dissemination may therefore have significant clinical implications. Lung dissemination and/or metastasis were investigated in mice carrying the polyomavirus middle-T oncogene (PyMT) during different stages of mammary tumorigenesis using the colony forming assay. Immunocytochemical or immunohistochemical staining was used to identify subpopulations of cells responsible for lung dissemination and metastasis. Histological examination was used to show primary and metastatic tumors. The tumor-initiating and metastatic capacity of cells expressing stem cell markers was assessed in syngeneic wild-type (WT) mice whose mammary fat pads were injected with these cells. Metastatic mammary epithelial cells were detected in the lungs of mice carrying the PyMT oncogene (MMT mice). These cells were observed early in breast tumorigenesis when the mammary tree appeared by histological inspection to be normal (or at a premalignant stage), suggesting the possession of disseminating and metastatic capacity even before full malignant transformation. Some of the disseminated cells and lung metastases displayed surface stem cell markers. These findings suggest that stem cells from apparently precancerous primary lesions could be a source of metastasis. Indeed, injection of lung tissue cells from MMT mice into syngeneic WT mice resulted in the formation of mammary tumors. These tumors resembled their parent mammary tumors in the MMT donors as well as grafted tumors derived from mammary tumor cells. Furthermore, when we injected lung tissue cells from GFP MMT mice into the fat pads of recipient WT mice, disseminated or metastatic GFP-expressing cells were detected in the lungs, lymph nodes and blood of the recipient WT mice. We finally identified a subpopulation of mammary epithelial/tumor cells expressing CD44 and Sca1 that was largely responsible for dissemination and metastasis in MMT mice. The tumorigenic and metastatic potential of a subpopulation of mammary epithelial/tumor cells in MMT mice is endowed relatively early in mammary neoplasms and suggests a potential role for cancer stem cell sub-populations in metastasis.
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影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
8.4
作者：
Engel, J;Eckel, R;Hölzel, D
通讯作者：
Hölzel, D
影响因子：
8
作者：
Jaskelioff, M.;Song, W.;Gong, J.
通讯作者：
Gong, J.
影响因子：
7.4
作者：
Damonte, Patrizia;Hodgson, J. Graeme;Borowsky, Alexander D.
通讯作者：
Borowsky, Alexander D.
DOI：
10.1126/science.1161621
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Podsypanina K;Du YC;Jechlinger M;Beverly LJ;Hambardzumyan D;Varmus H
通讯作者：
Varmus H