Mechanisms of disease: Breast tumor pathogenesis and the role of the myoepithelial cell

Breast cancer and precancer cells are influenced by important paracrine regulation from the breast microenvironment, which might be as great a determinant of breast cancer behavior as the specific oncogenic or tumor-suppressive alterations occurring within malignant breast cells. Myoepithelial cells exert profound effects on breast tumor cell behavior, and lie in juxtaposition to abnormally proliferating breast epithelial cells in precancerous disease states such as ductal carcinoma in situ (DCIS). Myoepithelial cells also form a natural border separating breast epithelial cells from stromal angiogenesis. These anatomical relationships suggest that myoepithelial cells might inhibit both the progression of DCIS to invasive breast cancer, and carcinoma-induced angiogenesis. Our ability to study myoepithelial cells has been fostered by recent technical advances in cell selection and sorting procedures, improved selective media, and high throughput technologies, which are able to assess the gene and protein expression profiles within cells. In addition, the establishment of a number of immortalized cell lines and xenografts of myoepithelial cells derived from benign human myoepithelial tumors of diverse sources has provided a self-renewing cell source through which to study the phenotype of myoepithelial cells. Studies of primary and immortalized myoepithelial cell lines indicate that these cells exhibit a natural tumor suppressor function. Functional studies show that these cells have anti-invasive and antiangiogenic phenotypes.