A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response

Publication date: Available online 3 March 2016
Source:Cancer Cell
Author(s): George Sflomos, Valerian Dormoy, Tauno Metsalu, Rachel Jeitziner, Laura Battista, Valentina Scabia, Wassim Raffoul, Jean-Francois Delaloye, Assya Treboux, Maryse Fiche, Jaak Vilo, Ayyakkannu Ayyanan, Cathrin Brisken
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.

Graphical abstract

Teaser

Sflomos et al. show that engrafting human estrogen receptor α-positive breast tumors into mouse milk ducts, in contrast to mammary fat pads, efficiently generates retransplantable xenografts that mimic the original tumors. They identify differential induction of SLUG by these microenvironments as a key factor.


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