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
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
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."