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Transition in cell type parallels treatment response, disease progression in breast cancer
Date:1/31/2013

and triple-negative tumors the assay revealed a small number of epithelial cells that also expressed mesenchymal markers. The investigators then conducted EMT analysis of circulating tumors cells (CTCs) cells that break off from solid tumors and travel through the bloodstream using the second-generation CTC-chip device developed in collaboration with the MGH Center for Engineering in Medicine.

Analysis of blood samples from 41 patients with metastatic breast cancer at various stages of their treatment identified CTCs expressing mesenchymal markers (M+) in samples from 16 patients. Pre- and post-treatment samples were available from 10 patients, 5 who had responded to treatment and 5 who had not. While post-treatment samples from patients whose tumors responded showed either an overall drop in the number of CTCs captured or fewer M+ cells, samples from patients whose tumors did not respond showed an increased proportion of M+ CTCs.

The investigators had access to serial blood samples taken from one patient at various stages during the course of her disease, which included initial response to an experimental treatment, followed by treatment resistance, subsequent response to another protocol and then resumed tumor progression. Both the number of CTCs and the proportion of cells with mesenchymal markers to those with epithelial markers dropped when her tumor responded to treatment and then rose when the disease progressed. The researchers also observed that an increase in M+ CTCs in this patient was associated with the appearance of multicellular clusters of CTCs, which conflicts with the predominant model of EMT inducing single tumor cells to migrate into the bloodstream, and they found evidence that the growth factor TGF-beta may mediate EMT in cancer.

"This study provides us with a new biologic understanding of breast cancer invasion and metastasis," says Daniel Haber, MD, PhD, director of the MGH Cancer Center and co-correspo
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Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert

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