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| Content Provider | Springer Nature Link |
|---|---|
| Author | Laurens, Nancy Engelse, Marten A. Jungerius, Clarissa Löwik, Clemens W. Hinsbergh, Victor W. M. Koolwijk, Pieter |
| Copyright Year | 2009 |
| Abstract | The fibrinous exudate of a wound or tumor stroma facilitates angiogenesis. We studied the involvement of RGD-binding integrins during tube formation in human plasma-derived fibrin clots and human purified fibrin matrices. Capillary-like tube formation by human microvascular endothelial cells in a 3D plasma-derived fibrinous matrix was induced by FGF-2 and TNF-α and depended largely on cell-bound u-PA and plasmin activities. While tube formation was minimally affected by the addition of either the αvβ3-integrin inhibiting mAb LM609 or the α5-integrin inhibiting mAb IIA1, the general RGD-antagonist echistatin completely inhibited this process. Remarkably, when αvβ3- and α5β1-integrins were inhibited simultaneously, tube formation was reduced by 78%. It was accompanied by a 44% reduction of u-PA antigen accumulation and 41% less production of fibrin degradation products. αvβ5-integrin-blocking antibodies further enhanced the inhibition by mAb LM609 and mAb IIA1 to 94%, but had no effect by themselves. αv-specific cRGD only inhibited angiogenesis when α5β1-integrin was simultaneously blocked. Endostatin mimicked the effect of α5β1-integrin and inhibited tube formation only in the presence of LM609 or cRGD (73 and 80%, respectively). Comparable results were obtained when purified fibrin matrices were used instead of the plasma-derived fibrinous matrices. These data show that blocking of tube formation in a fibrinous exudate requires the simultaneous inhibition of αvβ3- and α5β1-integrins. This may bear impact on attempts to influence angiogenesis in a fibrinous environment. |
| Starting Page | 275 |
| Ending Page | 285 |
| Page Count | 11 |
| File Format | |
| ISSN | 09696970 |
| Journal | Angiogenesis |
| Volume Number | 12 |
| Issue Number | 3 |
| e-ISSN | 15737209 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2009-05-16 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Angiogenesis αvβ3-integrin α5β1-integrin LM609 Endostatin Oncology Ophthalmology Cardiology Cell Biology Biomedicine general Cancer Research |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Clinical Biochemistry Cancer Research |
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