Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
Primary tumors facilitate metastasis by directing bone marrowderived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 39; pp. 16369 - 16374 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
27.09.2011
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Primary tumors facilitate metastasis by directing bone marrowderived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b⁺ BMDC recruitment and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression. |
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| AbstractList | Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b
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BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1–dependent event during breast cancer progression. Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b+ BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression. [PUBLICATION ABSTRACT] Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b + BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1–dependent event during breast cancer progression. Primary tumors facilitate metastasis by directing bone marrowderived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b⁺ BMDC recruitment and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression. Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b(+) BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression.Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b(+) BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression. |
| Author | Wirtz, Denis Wong, Chun-Ming Semenza, Gregg L. Chaturvedi, Pallavi Chen, Jasper Wong, Carmen Chak-Lui Zhang, Huafeng Fraley, Stephanie I. Gilkes, Daniele M. Khoo, Ui-Soon Ng, Irene Oi-Lin Wei, Hong |
| Author_xml | – sequence: 1 givenname: Carmen Chak-Lui surname: Wong fullname: Wong, Carmen Chak-Lui – sequence: 2 givenname: Daniele M. surname: Gilkes fullname: Gilkes, Daniele M. – sequence: 3 givenname: Huafeng surname: Zhang fullname: Zhang, Huafeng – sequence: 4 givenname: Jasper surname: Chen fullname: Chen, Jasper – sequence: 5 givenname: Hong surname: Wei fullname: Wei, Hong – sequence: 6 givenname: Pallavi surname: Chaturvedi fullname: Chaturvedi, Pallavi – sequence: 7 givenname: Stephanie I. surname: Fraley fullname: Fraley, Stephanie I. – sequence: 8 givenname: Chun-Ming surname: Wong fullname: Wong, Chun-Ming – sequence: 9 givenname: Ui-Soon surname: Khoo fullname: Khoo, Ui-Soon – sequence: 10 givenname: Irene Oi-Lin surname: Ng fullname: Ng, Irene Oi-Lin – sequence: 11 givenname: Denis surname: Wirtz fullname: Wirtz, Denis – sequence: 12 givenname: Gregg L. surname: Semenza fullname: Semenza, Gregg L. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21911388$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Biological Sciences Bone marrow Bone marrow cells Breast cancer breast neoplasms Breast Neoplasms - pathology Cancer Cell Line, Tumor Cell lines Collagen Collagen - metabolism Collagens crosslinking Family members Female Gene Knockdown Techniques Humans Hypoxia Hypoxia-Inducible Factor 1 - genetics Hypoxia-Inducible Factor 1 - physiology Lungs Metastasis mice Neoplasm Metastasis Rodents Tumors |
| Title | Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation |
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