Metastasis is an Early Event in Mouse Mammary Carcinomas and is Associated with Cells Bearing Stem Cell Markers

DSpace/Manakin Repository

Metastasis is an Early Event in Mouse Mammary Carcinomas and is Associated with Cells Bearing Stem Cell Markers

Citable link to this page

 

 
Title: Metastasis is an Early Event in Mouse Mammary Carcinomas and is Associated with Cells Bearing Stem Cell Markers
Author: Weng, Desheng; Penzner, Jeffrey H; Song, Baizheng; Koido, Shigeo; Gong, Jianlin; Calderwood, Stuart K.

Note: Order does not necessarily reflect citation order of authors.

Citation: Weng, Desheng, Jeffrey H. Penzner, Baizheng Song, Shigeo Koido, Stuart K. Calderwood, and Jianlin Gong. 2012. Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Research 14(1): R18.
Full Text & Related Files:
Abstract: Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
Published Version: doi:10.1186/bcr3102
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496135/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579216
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters