Tissue microenvironment is critical for the growth of ER+ breast cancer cells
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Mammary stroma induces TGFβ/SLUG signaling and basal differentiation in MCF7 cells
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Mouse milk ducts enable physiological growth of ER+ breast cancer cells
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Mouse intraductal ER+ PDXs are robust, retransplantable, and predictive
Summary
Seventy-five percent of breast cancers are estrogen receptor α positive (ER+). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER+ tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER+ tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER+ PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.
