title: Novel ERα positive breast cancer model with estrogen independent growth in the bone microenvironment.
abstract: Despite successful therapeutic options for estrogen receptor-α (ERα)+ breast cancer, resistance to endocrine therapy frequently occurs leading to tumor recurrence. In addition to intrinsic changes in the cancer cells, herein we demonstrate that tumor cell-microenvironment interactions can drive recurrence at specific sites. By using two ERα+ cell lines derived from spontaneous mammary carcinomas in STAT1-/- mice (SSM2, SSM3), we establish that the bone microenvironment offers growth advantage over primary site or lung in the absence of ovarian hormones. While SSM3 did not engraft at primary and skeletal locations in the absence of estrogen, SSM2 selectively grew in bone of ovariectomized mice and following administration of aromatase inhibitors. However, SSM2 growth remained hormone-dependent at extraskeletal sites. Unexpectedly, bone-residing SSM2 cells retained ERα expression and JAK2/STAT3 activation regardless of the hormonal status. These data position the bone microenvironment as a unique site for acquisition of tumor/estrogen independency and identify the first ERα+ hormone-independent tumor model in immunocompetent mice.
authors.affiliation: Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA.|Present address: Genentech, South San Francisco, CA, USA.
authors.forename: Aude-Hélène
authors.initials: AH
authors.lastname: Capietto
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.|Present address: Janssen Research and Development, Johnson and Johnson, Spring House, PA, USA.
authors.forename: Szeman Ruby
authors.initials: SR
authors.lastname: Chan
authors.affiliation: Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Ricci
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Allen
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Xinming
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.|Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.affiliation: Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Faccio
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D010053:Ovary / Q000378:metabolism; D010641:Phenotype; D011980:Receptors, Progesterone / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011980:Receptors, Progesterone
keywords: bone; breast cancer; endocrine resistance; hormone resistance; skeletal metastasis