Identification of a minority population of LMO2<sup>+</sup>breast cancer cells that integrate into the vasculature and initiate metastasis-Reference-Cited by-同舟云学术

Identification of a minority population of LMO2⁺breast cancer cells that integrate into the vasculature and initiate metastasis

Published:2022-11-11 Issue:45 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Sikandar Shaheen S.¹^ORCID,Gulati Gunsagar S.²,Antony Jane²^ORCID,Fetter Isobel¹^ORCID,Kuo Angera H.²^ORCID,Ho William Hai Dang²^ORCID,Haro-Acosta Veronica¹^ORCID,Das Soumyashree³,Steen Chloé B.⁴^ORCID,Pereira Thiago Almeida²^ORCID,Qian Dalong²^ORCID,Beachy Philip A.²^ORCID,Dirbas Fredrick⁵^ORCID,Red-Horse Kristy²³⁶^ORCID,Rabbitts Terence H.⁷^ORCID,Thiery Jean Paul⁸,Newman Aaron M.²⁹^ORCID,Clarke Michael F.²¹⁰^ORCID

Affiliation:

1. Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, School of Medicine, Stanford, CA 94305, USA.

3. Department of Biology, Stanford University, Stanford, CA 94305, USA.

4. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.

5. Department of Surgery, Stanford Cancer Institute, Stanford University School of Medicine, 875 Blake Wilbur Drive, Rm CC2235, Stanford, CA 94305, USA.

6. Howard Hughes Medical Institute, Stanford, CA 94305, USA.

7. Division of Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.

8. Guangzhou Laboratory, International Biological Island, Guangzhou, Guangdong 510005, China.

9. Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.

10. Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Abstract

Metastasis is responsible for most breast cancer–related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immatureTHY1+/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 ofLMO2+basal cells correlated with tumor endothelial content and predicted poor distant recurrence–free survival in patients. UsingMMTV-PyMT/Lmo2CreERT2mice, we demonstrated thatLmo2lineage–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 tumor necrosis factor–α and interleukin-6. 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference66 articles.

1. Cancer statistics, 2022

2. Cancer statistics, 2011

3. Emerging strategies for treating metastasis

4. Epithelial-Mesenchymal Plasticity in Cancer Progression and Metastasis

5. E-cadherin is required for metastasis in multiple models of breast cancer

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