Cited by 1,231Cancer Cells and MetastasisImmune cells in cancerMechanisms of cancer metastasis

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Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

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Erler, Janine T., Bennewith, Kevin L., Cox, Thomas R., Lang, Georgina, Bird, Demelza, Koong, Albert, Le, Quynh-Thu, Giaccia, Amato J.·2009·Cancer Cell

DOI 10.1016/j.ccr.2008.11.012PMC PMC3050620

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Abstract

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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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.
ORCID: Erler, Janine T.
Bennewith, Kevin L.
Cox, Thomas R.
Koong, Albert
Le, Quynh-Thu
Giaccia, Amato J.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2009-01
Volume: 15
Issue: 1
Pages: 35-44
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2008.11.012
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1658 d)
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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Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

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