Loss of Protective Barrier May Link DCIS to Invasive Breast Cancer

By Charles Bankhead
BOSTON, 06 may 2008-- Ductal carcinoma in situ progresses to invasive breast cancer because of the loss of a protective cellular barrier, leading to fibroblast-induced disintegration of milk duct walls, investigators here reported.
The findings provided insight into the mechanism of how DCIS transitions into invasive cancer. Molecular profiling studies comparing DCIS and invasive cancer have failed to explain the transformation the authors said.
"These findings made it clear that fibroblasts promote tumor growth and invasion and normal myoepithelial cells suppress it," said Dr. Polyak.
Myoepithelial cells inhibit tumor cell growth, invasion, and angiogenesis. During the progression of DCIS to invasive cancer, the inhibitory activity dissipates before disappearing altogether, Dr. Polyak and colleagues said.
To examine the effect of tumor microenvironment on disease progression, the investigators used the DCIS model MCFDCIS, which spontaneously progresses from a DCIS-like state to invasive cancer. They conducted a series of experiments wherein MCFDCIS was introduced into mice, along with either myoepithelial cells or fibroblasts.
When MCFDCIS was injected with myoepithelial cells, DCIS-like lesions arose, but the lesions were confined to the milk ducts. Repeating the experiments with MCFDCIS and fibroblasts, the investigators found that the resulting tumors invaded the walls of the ducts and subsequently escaped into surrounding tissue.
Additional studies focused on gene expression and signaling associated with progression from DCIS to invasive cancer. The observed abnormal activity in several myoepithelial-cell genes, including tumor growth factor-beta, Hedgehog, p63, and several genes involved in myoepithelial-cell adhesion to basement cells on milk ducts' exterior wall.
"We found a constant, complex interplay of signals among these genes, both within myoepithelial cells themselves, and between myoepithelial cells and their neighbors," said Dr. Polyak. "The presence of DCIS causes the pattern of signals to change significantly, upsetting the normal development of myoepithelial cells."
The findings suggest the possibility that examining myoepithelial tissue for genetic abnormalities could identify patients with the greatest risk of progression from DCIS to invasive breast cancer, she added.
Dr. Polyak reported no disclosures.
Primary source: Cancer CellSource reference:Hu Min, et al "Regulation of in situ to invasive breast carcinoma transition"Cancer Cell. 2008; 13: DOI: 10.1016/j.ccr.2008.03.007.Additional Breast Cancer Coverage