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Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche
Open accessAbstract
Tumor cell metastasis is facilitated by "premetastatic niches" formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to crosslinked collagen IV and produce matrix metalloproteinase-2, which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also colocalize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.
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“Specifically, hypoxia-induced lysyl oxidase contributes to the pre-metastatic niche in a process that includes collagen crosslinking and recruitment of CD11b + myeloid cells (Erler et al., 2009).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Erler et al., 2009
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“The BMDCs promote metastasis by producing chemokines that recruit tumor cells to the lung by mechanisms that include stimulation of tumor cell extravasation”
From Hypoxic control of metastasis (2016) · cites this paper as [92]
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Metadata
- Authors
- Erler, J. T., Bennewith, K. L., Cox, T. R., Lang, G., Bird, D., Koong, A., Le, Q.-T., & Giaccia, A. J.
- Affiliations
- Institute of Cancer Research (GB)
- BC Cancer Agency (CA)
- Stanford Medicine (US)
- Corresponding author
- Giaccia, Amato J.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 15
- Issue
- 1
- Pages
- 35-44
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3050620
- OpenAlex
- W2159744630
- Cited by
- 1,231
- References
- 40
- Citations by year
- 2026: 38 · 2025: 45 · 2024: 61 · 2023: 66 · 2022: 62 · 2021: 82 · 2020: 78 · 2019: 96 · 2018: 80 · 2017: 71 · 2016: 90 · 2015: 72 · 2014: 74 · 2013: 87 · 2012: 72
- FWCI
- 37.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK
- National Cancer Institute (P01CA067166, T32CA009151)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- lysyl oxidase, pre-metastatic niche, metastasis, bone marrow-derived cells, hypoxia, breast cancer, CD11b+ myeloid cells, basement membrane, MMP-2, collagen degradation, metastasis prevention
- MeSH terms
- Animals, Hypoxia, Basement Membrane, Bone Marrow Cells, Breast Neoplasms, Cell Differentiation, Cell Movement, Cell Separation, Enzyme Activation, Humans, Lung Neoplasms, Protein-Lysine 6-Oxidase, Mice, Nude, Neoplasm Metastasis, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Disease Progression, Matrix Metalloproteinase 2, Myeloid Cells, Xenograft Model Antitumor Assays, Collagen Type IV, Cell Line, Tumor, Mice
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