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An intra-ductal human-in-mouse (HIM) transplantation model mimics the subtypes of ductal carcinoma in situ
Dr. Fariba Behbod Department of Pathology and Laboratory Medicine
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Human models of non-invasive breast cancer lesions are limited. Furthermore, the existing in vivo models do not mimic human breast cancer heterogeneity. Dr. Behdod's goal is to design an in vivo model whereby distinct mechanisms of malignant progression could be studied in various subtypes of non-invasive human breast cancers. To accomplish this goal, Dr. Behbod has recently adopted an intra-ductal transplantation model. This involves injection of human breast cancer cells directly into the primary mouse mammary ducts. The intra-ductal transplant model allows one to observe how cancer cells invade into the stroma by traversing natural boundaries provided by an intact myoepithelium and basement membrane, thus mimicking DCIS progression in the human breast. This method has been efficient for growing ductal carcinoma in situ (DCIS) cell lines (MCF10DCIS.COM, and SUM-225) and a limited success with a primary human DCIS (FSK-H7). DCIS.COM generates a basal class lesion, whereas SUM-225 and FSK-H7 generate Her-2 over-expressing DCIS-like lesions. By utilizing this model, Dr. Behbod has shown that various subtypes of human DCIS contain distinct subpopulations with increased intra-ductal growth potential. Assuming that increased growth (and perhaps self-renewal) potential correlates with an increased risk for malignant progression, various subtypes of human breast non-invasive lesions may need to be individually targeted for prevention of invasive progression. Thus, intra-ductal transplantation is a valid tool to mimic human breast cancer heterogeneity at the non-invasive stages and to study the distinct molecular and cellular mechanisms of breast cancer malignant progression. |