New Paradigm for African American Breast Cancer Involving Stem Cell Differentiation in a Novel Cell Culture System

摘要

Our laboratory has published a novel culture system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for unusually long-term establishment of normal primary cultures that begin as three-dimensional 'mammospheres,' which subsequently differentiate into complex organotypic branching ducts and lobules that demonstrate Epithelial Specific Antibody (ESA) staining, lumen, polarized nuclei, desmosomes along the lateral surfaces of the cells, and microvilli on the apical surfaces. We hypothesize that since we have demonstrated de novo formation of multicellular organotypic epithelial ductal and lobular structures, that our cultures must contain multipotent stem cells. We have established primary HMEC cultures from 35/35 breast reduction mammoplasty tissues. These tissues included: 19 pre-menopausal, 9 post-menopausal and 7 peri-menopausal (ages 45-55) subjects. Six out of 35 of the subjects from whom this tissue came, were African American and matched in socioeconomic status with the white women (middle class). We found: 1. The more children a woman had, the less likely her breast tissue was to form ductal structures in vitro consistent with the idea that lactational differentiation decreases the number of pluripotent stem cells in the breast. 2. Pre-menopausal breast tissue was more likely to form ductal structures in culture than post- menopausal tissue. 3. Race was shown to contribute as a modifying factor in the ability to form ductal architecture in culture, with AA tissue demonstrating more of an ability to spontaneously differentiate than white tissue.