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Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation.

Evans, Colin E; Bendahl, Pär-Ola LU ; Belting, Mattias LU ; Branco, Cristina and Johnson, Randall S (2016) In Blood 127(10). p.1355-1360
Abstract
Despite the increased risk of thrombosis in cancer patients compared with healthy individuals, mechanisms that regulate cancer-induced hypercoagulation are incompletely understood. The aim of this study was to investigate whether cell-specific hypoxia-inducible factor (HIF) 1α regulates cancer-associated hypercoagulation, using in vitro clotting assays and in vivo cancer models. In mouse lung and mammary tumor cells, hypoxia led to increases in cell adhesion, clotting, and fibrin deposition; these increases were eliminated in HIF1α null cells. Increased levels of HIF1α were also associated with increased tissue factor expression in human breast tumor samples. Conversely, deletion of endothelial (but not myeloid) cell-specific HIF1α doubled... (More)
Despite the increased risk of thrombosis in cancer patients compared with healthy individuals, mechanisms that regulate cancer-induced hypercoagulation are incompletely understood. The aim of this study was to investigate whether cell-specific hypoxia-inducible factor (HIF) 1α regulates cancer-associated hypercoagulation, using in vitro clotting assays and in vivo cancer models. In mouse lung and mammary tumor cells, hypoxia led to increases in cell adhesion, clotting, and fibrin deposition; these increases were eliminated in HIF1α null cells. Increased levels of HIF1α were also associated with increased tissue factor expression in human breast tumor samples. Conversely, deletion of endothelial (but not myeloid) cell-specific HIF1α doubled pulmonary fibrin deposition, and trebled thrombus formation compared with wildtype littermates in tumor-bearing mice. Our data suggest that tumor and endothelial cell-specific HIF1α may have opposing roles in cancer-associated coagulation and thrombosis. Off-target effects of manipulating the HIF1 axis in cancer patients should be carefully considered when managing thrombotic complications. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
127
issue
10
pages
5 pages
publisher
American Society of Hematology
external identifiers
  • pmid:26702059
  • scopus:84960852821
  • wos:000373501700020
ISSN
1528-0020
DOI
10.1182/blood-2015-09-671982
language
English
LU publication?
yes
id
727fde3a-3e33-496c-a1b9-7805f5c05a95 (old id 8503745)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26702059?dopt=Abstract
date added to LUP
2016-01-06 13:22:50
date last changed
2017-06-18 04:39:13
@article{727fde3a-3e33-496c-a1b9-7805f5c05a95,
  abstract     = {Despite the increased risk of thrombosis in cancer patients compared with healthy individuals, mechanisms that regulate cancer-induced hypercoagulation are incompletely understood. The aim of this study was to investigate whether cell-specific hypoxia-inducible factor (HIF) 1α regulates cancer-associated hypercoagulation, using in vitro clotting assays and in vivo cancer models. In mouse lung and mammary tumor cells, hypoxia led to increases in cell adhesion, clotting, and fibrin deposition; these increases were eliminated in HIF1α null cells. Increased levels of HIF1α were also associated with increased tissue factor expression in human breast tumor samples. Conversely, deletion of endothelial (but not myeloid) cell-specific HIF1α doubled pulmonary fibrin deposition, and trebled thrombus formation compared with wildtype littermates in tumor-bearing mice. Our data suggest that tumor and endothelial cell-specific HIF1α may have opposing roles in cancer-associated coagulation and thrombosis. Off-target effects of manipulating the HIF1 axis in cancer patients should be carefully considered when managing thrombotic complications.},
  author       = {Evans, Colin E and Bendahl, Pär-Ola and Belting, Mattias and Branco, Cristina and Johnson, Randall S},
  issn         = {1528-0020},
  language     = {eng},
  number       = {10},
  pages        = {1355--1360},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation.},
  url          = {http://dx.doi.org/10.1182/blood-2015-09-671982},
  volume       = {127},
  year         = {2016},
}