Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche

By J. Erler, K. Bennewith, T. Cox, G. Lang, D. Bird, A. Koong, Quynh-Thu Le, Amato J. Giaccia. Cancer Cell, 2009

1,212 citations recorded by the source corpus.

Summary Tumor cell metastasis is facilitated by “pre-metastatic niches” formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for pre-metastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at pre-metastatic sites, cross-links collagen-IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to cross-linked 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 co-localize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in pre-metastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.

Subfields: Cancer Research, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3f8837a1495a468a0867333f63ee3efc2ff8d416

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Citations in the corpus

The Cancer Stem Cell Niche: How Essential is the Niche in Regulating Stemness of Tumor Cells? (2015, positive): “The metastatic niches are populated by Gr1+ CD11b+ myeloid cells recruited by LOX and S100A proteins (Erler et al., 2009; Psaila and Lyden, 2009; Yan et al., 2010).”
Macrophages, innate immunity and cancer: balance, tolerance, and diversity. (2010, background): “Tumor cell products, including extracellular matrix components, IL-10, CSF-1, activate macrophages and set them in an M2, cancer promoting mode [33 ,34–36].”
Hypoxia and hypoxia-inducible factors (HIFs): master regulators of metastasis (2010, background): “Interestingly, a critical mobilizing factor is LOX, a known hypoxia target, which recruits CD11bþ myeloid cells to form the niche to facilitate the colonization of metastatic tumor cells (31).”
Hallmarks of cancer: interactions with the tumor stroma. (2010, background): “by activation of bone marrow-derived cells that contribute to the formation of a pre-metastatic niche in distant organs [67,68].”
Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, neutral): “According to this model, primary tumors release systemic signals, perhaps including lysyl oxidase (LOX) (Erler et al., 2009), that induce organ-specific upregulation of fibronectin from resident tissue fibroblasts.”
Tumor entrained neutrophils inhibit seeding in the premetastatic lung (2011, positive): “Recent studies have suggested that factors secreted from the primary tumormaymodulate the future site of metastasis in a directed fashion (Erler et al., 2009).”
Microenvironmental regulation of metastasis (2009, background): “This fibronectin deposition, together with other ECM molecules, may also be increased by the secretion of enzymes such as lysyl oxidase from primary tumours acting on these distant fibroblast”
The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy (2015, background): “Inhibition of LOX reduced hypoxiainduced recruitment and metastasis in the breast cancer mouse model.(88) Another target candidate induced by hypoxia in cancer cells is CXCR4 involved in cell trafficking.”