Ubellacker, J.M., Baryawno, N., Severe, N. et al. (13 more authors) (2018) Modulating bone marrow hematopoietic lineage potential to prevent bone metastasis in breast cancer. Cancer Research , 78 (18). ISSN 0008-5472
Abstract
The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiological, pathological, and therapeutic conditions impact hematopoiesis, it remains unclear if targeting hematopoiesis presents opportunities for limiting bone metastasis. Using pre-clinical 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 random 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, American Association for Cancer Research. This is an author produced version of a paper subsequently published in Cancer Research. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number WESTON PARK HOSPITAL CANCER CHARITY CA150 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 10 Sep 2018 13:39 |
Last Modified: | 19 Apr 2024 11:40 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Refereed: | Yes |
Identification Number: | 10.1158/0008-5472.CAN-18-0548 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:135484 |