Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Bone Metastasis in Breast Cancer
| Autor: | Ingunn Holen, Walter M Gregory, Nicolas Severe, Sandra S. McAllister, Jaclyn Sceneay, Ninib Baryawno, Marie-Therese Haider, Catherine Rhee, David T. Scadden, Molly J. DeCristo, Robert E. Coleman, Yuanbo Qin, Ana C. Garrido-Castro, John N. Hutchinson, Janet E. Brown, Jessalyn M. Ubellacker |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Myeloid medicine.medical_treatment Mice Nude Osteoclasts Antineoplastic Agents Bone Marrow Cells Bone Neoplasms Breast Neoplasms Zoledronic Acid Article Metastasis Suppression Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Bone Marrow Osteoclast Cell Line Tumor Granulocyte Colony-Stimulating Factor Animals Humans Medicine Cell Lineage Neoplasm Metastasis business.industry Macrophages Bone metastasis Cell Differentiation Bisphosphonate Hematopoietic Stem Cells medicine.disease Hematopoiesis Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Zoledronic acid Oncology 030220 oncology & carcinogenesis Cancer research Female Bone marrow Neoplasm Recurrence Local business Biomarkers medicine.drug |
| Zdroj: | Cancer Research. 78:5300-5314 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-18-0548 |
| Popis: | The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiologic, pathologic, and therapeutic conditions impact hematopoiesis, it remains unclear whether targeting hematopoiesis presents opportunities for limiting bone metastasis. Using preclinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive. Specifically, ZA modulated hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to activate metastasis-suppressive activity. Granulocyte-colony stimulating factor (G-CSF) promoted ZA resistance by redirecting M/OCP differentiation. We identified M/OCP and bone marrow transcriptional programs associated with metastasis suppression and ZA resistance. Analysis of patient blood samples taken at randomization revealed that women with high-plasma G-CSF experienced significantly worse outcome with adjuvant ZA than those with lower G-CSF levels. Our findings support discovery of therapeutic strategies to direct M/OCP lineage potential and biomarkers that stratify responses in patients at risk of recurrence. Significance: Bone marrow myeloid/osteoclast progenitor cell lineage potential has a profound impact on breast cancer bone metastasis and can be modulated by G-CSF and bone-targeting agents. Cancer Res; 78(18); 5300–14. ©2018 AACR. |
| Databáze: | OpenAIRE |
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