Zoledronic acid alters hematopoiesis and generates breast tumor-suppressive bone marrow cells.
Background: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore m...
| Publicado en: | Breast Cancer Research Vol. 19; pp. 1 - 16 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
BioMed Central
3/6/2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=121780936&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 121780936 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 3/6/2017 vid: 19 pid: 24147 pub: BioMed Central artinfo: ui: 121780936 121780936 NLM28264701 121780936 10.1186/s13058-017-0815-8 NLM28264701 121780936 ppf: 1 ppct: 15 formats: fmt: @attributes: type: P tig: atl: Zoledronic acid alters hematopoiesis and generates breast tumor-suppressive bone marrow cells. aug: au: Ubellacker, Jessalyn M. Haider, Marie-Therese DeCristo, Molly J. Allocca, Gloria Brown, Nicola J. Silver, Daniel P. Holen, Ingunn McAllister, Sandra S. affil: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA sug: subj: Imidazoles Pharmacodynamics Diphosphonates Pharmacodynamics Hematopoiesis Drug Effects Breast Neoplasms Blood Bone Marrow Drug Effects Breast Neoplasms Metabolism Bone Marrow Metabolism Extracellular Space Macrophages Drug Effects Female Animal Studies Breast Neoplasms Pathology Bone Marrow Pathology Hematopoietic Stem Cells Drug Effects Tomography, X-Ray Computed Osteoblasts Metabolism Colony-Forming Units Assay Macrophages Metabolism Models, Biological Leukocyte Count Neovascularization, Pathologic Metabolism Bone and Bones Metabolism Hematopoietic Stem Cells Metabolism Osteoblasts Drug Effects Bone and Bones Pathology Breast Neoplasms Drug Therapy Neovascularization, Pathologic Drug Therapy Bone and Bones Bone Marrow Mice Cell Line, Tumor Funding Source Female ab: Background: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore may affect hematopoietic cells that play a role in breast cancer progression.Method: Immunocompetent and immunocompromised strains of mice commonly used for breast cancer research were injected with a single, clinically relevant dose of ZOL (100 μg/kg) or vehicle control. The effects of ZOL on the bone marrow microenvironment (bone volume, bone cell number/activity, extracellular matrix composition) were established at various time points following treatment, using micro-computed tomography (μCT) analysis, histomorphometry, ELISA and immunofluorescence. The effects on peripheral blood and bone marrow hematopoietic progenitor populations were assessed using a HEMAVET® hematology analyzer and multicolor flow cytometry, respectively. Tumor support function of bone marrow cells was determined using an in vivo functional assay developed in our laboratory.Results: Using multiple mouse strains, we observed transient changes in numbers of hematopoietic stem cells, myeloid-biased progenitor cells, and lymphoid-biased cells concurrent with changes to hematopoietic stem cell niches following ZOL administration. Importantly, bone marrow cells from mice treated with a single, clinically relevant dose of ZOL inhibited breast tumor outgrowth in vivo. The ZOL-induced tumor suppressive function of the bone marrow persisted beyond the time point at which numbers of hematopoietic progenitor cells had returned to baseline.Conclusions: These findings provide novel evidence that alterations to the bone marrow play a role in the anti-tumor activity of ZOL and suggest possibilities for capitalizing on the beneficial effects of ZOL in reducing breast cancer development and progression. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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