[PDF][PDF] Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche

JT Erler, KL Bennewith, TR Cox, G Lang, D Bird… - Cancer cell, 2009 - cell.com
JT Erler, KL Bennewith, TR Cox, G Lang, D Bird, A Koong, QT Le, AJ Giaccia
Cancer cell, 2009cell.com
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 …
Summary
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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