@article {1503179,
	title = {Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Bone Metastasis in Breast Cancer},
	journal = {Cancer Res},
	volume = {78},
	number = {18},
	year = {2018},
	month = {2018 09 15},
	pages = {5300-5314},
	abstract = {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. 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. .},
	keywords = {Animals, Antineoplastic Agents, Biomarkers, Bone Marrow, Bone Marrow Cells, Bone Neoplasms, Breast Neoplasms, Cell Differentiation, Cell Line, Tumor, Cell Lineage, Female, Granulocyte Colony-Stimulating Factor, Hematopoiesis, Hematopoietic Stem Cells, Humans, Macrophages, Mice, Mice, Inbred C57BL, Mice, Nude, Neoplasm Metastasis, Neoplasm Recurrence, Local, Osteoclasts, Zoledronic Acid},
	issn = {1538-7445},
	doi = {10.1158/0008-5472.CAN-18-0548},
	author = {Ubellacker, Jessalyn M and Baryawno, Ninib and Severe, Nicolas and DeCristo, Molly J and Sceneay, Jaclyn and Hutchinson, John N and Haider, Marie-Therese and Rhee, Catherine S and Qin, Yuanbo and Gregory, Walter M and Garrido-Castro, Ana C and Holen, Ingunn and Brown, Janet E and Coleman, Robert E and Scadden, David T and McAllister, Sandra S}
}
