Targeting Basal Breast Cancer
Abstract
We set out to determine 1) if Gpr specifically identifies mammary stem/progenitors; 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1120868
Entities
People
- Pamela Cowin
Organizations
- Grossman School of Medicine