Cancer Cell paper shows that mutations in myoepithelial cell genes cause the breakdown of this layer.
The cause for ductal carcinoma in situ (DCIS) invading spreading to other parts of the body lies not in the tumor cells themselves but in a group of abnormal surrounding cells, according to a group of scientists.
Researchers initially thought that DCIS might become invasive as a result of genetic changes in the cancer cells. When they surveyed gene activity in immobile DCIS cells and in those that had spread, however, they found no significant differences. Next, they injected MCFDCIS cells into laboratory animals. These cells formed DCIS-like tissue that developed into invasive tumors.
When both MCFDCIS and myoepithelial cells were injected into the mice, DCIS tumors arose but they were confined to the ducts. When MCFDCIS cells and fibroblasts were injected, the resulting DCIS tumors broke into the walls of the ducts.
Furthermore, the team found that when certain genes in the myoepithelial layer become under- or overactive, the layer breaks down and disappears, enabling tumor cells to escape. Specifically, they indetified the TGF Beta, Hedgehog, and p63 genes as well as genes that help myoepithelial cells stick to basement cells on the ducts’ outer layer.
The study was done by researchers from the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Biogen Idec, GeneGo, Washington University School of Medicine, Lawrence Berkeley National Laboratory, and Beth Israel Deaconess Medical Center. The study will be reported in the May 6 issue of Cancer Cell.