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Myoepithelial Cells May Be Key to Suppression of DCIS Growth

Myoepithelial Cells May Be Key to Suppression of DCIS Growth

LOS ANGELES--Laboratory studies from the UCLA School of Medicine point to a role for myoepithelial cells in suppressing breast cancer invasion, said researcher Mark Sternlicht, PhD. Myo-epithelial cells lie between the epithelium and the basement membrane. They synthesize and maintain the basement membrane and can promote epithelial differentiation. They are found surrounding benign and nonmalignant lesions.

"Myoepithelial cells rarely transform," Dr. Sternlicht said at the San Antonio Breast Cancer Symposium. "And when they do, they transform to benignity or low-grade neoplasms that do not invade and do not metastasize."

Surrogates Developed

Researchers at the UCLA laboratory, under the direction of Dr. Sanford Barsky, have developed cell lines and transplantable xenografts from benign myoepithe-lial tumors to serve as a surrogate to study the effects of myoepithelial cells on breast cancer invasion.

"These myoepithelial tumors are slow growing; it takes six months of nude mouse growth to reach about 1.5 cm in diameter," Dr. Sternlicht said. He noted that these tumors make an abundant extracellular matrix, composed of a number of basement membrane and non-basement membrane molecules.

More importantly, he said, myoepithe-lial cells express high levels of proteinase inhibitors and angiogenic inhibitors, and very low levels of proteinase and no angiogenic-stimulating factors. Many of these proteinase and angiogenic inhibitors can be seen selectively in tissue sections of ductal carcinoma in situ (DCIS) in the surrounding myoepithelial layer.

One of the myoepithelial cell lines, HMS1, has been shown in vitro to dramatically inhibit tumor invasion and angiogenesis (endothelial cell migration and mitogenesis). The UCLA work further suggests that the anti-invasive effect is mediated in part through maspin, a member of the serpin superfamily of proteinase inhibitors, while the angiogenic inhibition is mediated primarily through thrombospondin-1.

With all of this evidence for the "myoepithelial defense," Dr. Sternlicht hypothesizes that DCIS is regulated by the paracrine interaction of the myoepi-thelial cells and "this is why DCIS stays confined for so many years and why there is no demonstrable genetic alteration between DCIS and invasive cancer."

 
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