title: Estrogen promotes ER-negative tumor growth and angiogenesis through mobilization of bone marrow-derived monocytes.
abstract: Estrogen has a central role in the genesis and progression of breast cancers whether they are positive or negative for the estrogen receptor (ER). While therapies that disrupt estrogen biosynthesis or ER activity can treat these diseases in postmenopausal women, in younger women where ovarian function remains intact, these anti-estrogen therapies are not as effective. Moreover, emerging clinical evidence suggests that estrogen may promote other cancers. Thus, circulating estrogens may participate in cancer pathogenesis in ways that are not yet understood. In this study, we show that estrogen can promote the outgrowth of murine xenograft tumors established from patient-derived ER-negative breast cancer cells by influencing the mobilization and recruitment of a proangiogenic population of bone marrow-derived myeloid cells. ERα expression was necessary and sufficient in the bone marrow-derived cells themselves to promote tumor formation in response to estrogen. Our findings reveal a novel way in which estrogen promotes tumor formation, with implications for the development and application of anti-estrogen therapies to treat cancer in premenopausal women.
authors.affiliation: Department of Anatomy & Cellular Biology, Sackler School of Biomedical Research, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Iyer
authors.forename: Ina
authors.initials: I
authors.lastname: Klebba
authors.forename: Jessica
authors.initials: J
authors.lastname: McCready
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Arendt
authors.forename: Monica
authors.initials: M
authors.lastname: Betancur-Boissel
authors.forename: Meng-Fen
authors.initials: MF
authors.lastname: Wu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lewis
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011960:Receptors, Estrogen / Q000032:analysis / Q000502:physiology*
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol