title: Role of Integrins α1β1 and α2β1 in Wound and Tumor Angiogenesis in Mice.
abstract: Integrins are transmembrane receptors composed of one α subunit and one β subunit and are involved in cellular growth, differentiation, and apoptosis. The collagen-binding integrins α1β1 and α2β1 have been shown to regulate wound and tumor vascularization by different mechanisms. In this study, we assessed wound and tumor vascularization in mice with genetic ablation of both integrin subunits α1 and α2, which resulted in loss of integrins α1β1 and α2β1. Wound angiogenesis was investigated in excisional wounds that were inflicted on the back skin of control and mice lacking integrin α1β1 and α2β1. Mutant mice displayed reduced wound angiogenesis, which correlated with decreased macrophage numbers at 3 and 7 days after injury, and showed significantly attenuated vascularization of sponge implants. Angiogenesis induced by tumors arising from intradermal injection of B16 F1 melanoma cells was also reduced in comparison to controls 7 days after injection. This reduction in angiogenesis correlated with increased levels and activity of circulating matrix metalloproteinase 9 and elevated angiostatin levels in plasma of mutant mice, which reduced endothelial cell proliferation. Ex vivo mutant aortic ring explants developed significantly fewer and thinner aortic sprouts with fewer branch points than controls because of impaired endothelial cell proliferation. In conclusion, the loss of integrins α1β1 and α2β1 in mice results in reduced wound and tumor angiogenesis by cell-autonomous and extrinsic mechanisms.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Ghatak
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Niland
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Jan-Niklas
authors.initials: JN
authors.lastname: Schulz
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Eble
authors.affiliation: The Biotechnology Centre, University of Oslo, Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany. Electronic address: paola.zigrino@uni-koeln.de.
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany. Electronic address: beate.eckes@uni-koeln.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039222:Integrin alpha1beta1 / Q000235:genetics / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000098:blood supply* / Q000209:etiology / Q000473:pathology; D009389:Neovascularization, Pathologic; D012867:Skin / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000098:blood supply; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000209:etiology / Q000473:pathology*
chemical_list: D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1