Targeting Basal Breast Cancer
[Technical Report, Annual Report]
New York University School of Medicine
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We set out to determine 1 if Gpr specifically identifies mammary stemprogenitors and 2 the significance of Gpr expression in tumors and whether ablating Gpr cells would prevent or eradicate them. To test these hypotheses, we proposed to a identify, isolate and characterize Gpr cells, determine their potency by tracing their progeny, and monitor the effects of ablating them on mammary development b determine Gpr expression in human breast cancer, and test if ablating Gpr cells affects mammary tumorigenesis in mouse models. In this grant period we have 1 completed analysis of Gpr expression in the embryonic mammary gland 2 consolidated scRNAseq and immunofluorescence analysis of Gpr 3 completed lineage tracing of the progeny of embryonic, pubertal and pregnancy-induced Gpr cells 4 identified Gpr cells as migratory myoepithelial progenitors in other secretory organs 5 confirmed Gpr association with poor outcome in basal-type breast cancer 6 shown Gpr progenitors in MMTV-Wnt1 tumors retain embryonic mesenchymal features and potency. These results show that Gpr identifies mammary stem cells in the embryonic mammary gland and unipotent progenitors in perinatal and postnatal mammary gland. Gpr cells associated with early tumor onset are bipotent and share mesenchymal features with embryonic progenitors at invasive tips of the embryonic rudiment.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research