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6 May 2008
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Myoepithelial cell lining plays key role in DCIS breast cancer spread
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MedWire News: Whether or not an in situ breast tumor will progress to become invasive depends on the integrity of the cells lining the milk ducts, in particular genetic changes that occur in myoepithelial cells, say US researchers.
Kornelia Polyak (Dana-Farber Cancer Institute, Boston, Massachusetts) and colleagues say the transition of in situ to invasive breast carcinoma may not be due to the intrinsic properties of the tumor epithelial cells but rather "determined by complex interactions among all the cell types that compose the tumor microenvironment."
The researchers hope their work will set the stage for new therapeutic strategies, which will focus on these interactions and hopefully keep the nascent cancer contained.
Previous studies have found no significant difference in gene activity between immobile ductal carcinoma in situ (DCIS) cells and breast cancer cells that have spread and become invasive. Given the recent spate of research into the role of the tumor microenvironment in cancer biology, Polyak et al turned their attention to the cells that line the milk ducts.
The researchers used an engineered breast cancer cell line akin to DCIS and transplanted cells into a mouse to create a xenograft model of human breast cancer progression.
When DCIS cells were co-injected with healthy myoepithelial cells that line the milk ducts the cancer cells remained in situ and did not become invasive. By contrast, when DCIS cells were co-injected with fibroblast cells they progressed to form invasive tumors.
"These findings made it clear that fibroblasts promote tumor growth and invasion, and normal myoepithelial cells suppress it," Polyak et al remark.
The researchers then used a technique called serial analysis of gene expression (SAGE) to look for genetic changes and cell signal interactions that cause DCIS cells to become invasive.
Based on the SAGE results, Polyak et al say that transforming growth factor β, Hedgehog, and p63 signaling in myoepithelial cells may be crucial for their role in containing DCIS breast cancer.
The researchers conclude in the Journal of Clinical Oncology: "Our results not only highlight the importance of the microenvironment in breast tumor progression, but also point to the significance of the myoepithelial cell layer and basement membrane as gatekeepers of DCIS."
Cancer Cell 2008; 13: 394-406
http://www.cancercell.org/content/article/abstract?uid=PIIS1535610808000913
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© 2006 CMG
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