Data from: Identification of a minority population of LMO2+ breast cancer cells that integrate into the vasculature and initiate metastasis.
Creators
- 1. University of California, Santa Cruz
- 2. Stanford University
Description
Metastasis is responsible for the majority of breast cancer-related deaths, however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1+/VEGFA+ tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher abundance of LMO2+ basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by TNFα and IL6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.
Notes
All data are stored as tab-delimited text files that can be opened with any spreadsheet software program. All code was written in either R or bash.
Funding provided by: Breast Cancer Research Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100001006
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Funding provided by: Stanford Bio-X Interdisciplinary Initiatives Seed 809 Grants Program*
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Funding provided by: Virginia and D.K. Ludwig Fund for Cancer 810 Research*
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Funding provided by: Stinehart-Reed Foundation*
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Funding provided by: Stanford School of Medicine Dean's Fellowship*
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Funding provided by: Stanford Bio-X Bowes Graduate Student Fellowship*
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Funding provided by: Stanford Medical Science Training Program*
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Funding provided by: New 813 York Stem Cell Foundation – Robertson Investigator*
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Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01 - HL128503
Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: U01CA154209-01
Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: U01CA154209-01
Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: P01 CA139490-05
Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: P01 CA139490-05
Funding provided by: U.S. Department of Defense
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000005
Award Number: W81XWH-11-1-0287
Funding provided by: U.S. Department of Defense
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000005
Award Number: W81XWH-13-1-0281
Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: 00CA187192-03
Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: 5R01CA100225-09
Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: PHS grant no. CA09302
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Additional details
Related works
- Is cited by
- 10.1101/2021.05.26.443198 (DOI)
- Is source of
- 10.5061/dryad.stqjq2c6j (DOI)