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Berkeley Lab scientists find that normal breast cells help kill cancer cells
Date:4/13/2011

if they were normal breast cells. Similar results were also achieved with certain cell signaling inhibitors.

Says Bissell, "These observation suggested that acinus-forming nonmalignant mammary epithelial cells secrete factors that can suppress the phenotype of breast cancer cells growing in 3D cultures. We hypothesized that such a complex phenotypical reversion is likely the result of multiple signaling factors that in combination allow cancer cells to form quiescent acinar-like structures. We sought to identify and characterize these factors using solubility and size-fractionation of the conditioned medium from normal mammary epithelial cells, along with functional assays to identify the active molecules."

Fractionating the conditioned medium first by solubility revealed that its tumor suppressive activity could be divided into a morphogenic insoluble fraction and a cytotoxic soluble fraction. Fractionating this cytotoxic soluble portion according to molecule size revealed that the most potent tumor cellkilling activity took place in the 10-to 50-kiloDalton range, which would be something the size of a protein. Mass spectrometry was then used to identify the cytokine IL25 as the protein with the most potent cytotoxic activity. Subsequent functional assays revealed that IL25 interacts with the IL25 receptor to activate apoptosis (cell death).

"We analyzed randomized cohorts of breast biopsy samples and found that 20-percent of the breast cancer samples tested were IL25 receptor-positive," Furuta says. "Importantly, these IL25 receptor-positive tumors were highly invasive and correlated to poor clinical outcome patients. We believe that in the future the IL25 receptor will serve as a novel therapeutic marker for breast cancer diagnosis and treatment."

Furuta says she and Bissell and their colleagues are now looking at five other proteins they discovered being secreted by normal developing breast cells. While these other protein
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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