Plasmin‐driven fibrinolysis facilitates skin tumor growth in a gender‐dependent manner
| Autor: | Rasmus Baadsgaard Maerkedahl, Lars H. Engelholm, Kristoffer L. Egerod, Hanne Eickhardt, Leif R. Lund, Andreas Hald, Ole Didrik Laerum, Birgitte Rønø, Christina Winther Feldborg |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Skin Neoplasms Plasmin Ovariectomy medicine.medical_treatment Fibrinogen Biochemistry Fibrin Mice Sex Factors Fibrinolysis Genetics medicine Animals Humans Fibrinolysin Keratinocyte migration Molecular Biology Mice Knockout biology Chemistry Thrombosis Neoplasms Experimental medicine.disease Extracellular Matrix Gene Expression Regulation Neoplastic Cancer research biology.protein Female Tumor necrosis factor alpha Laminin Skin cancer Wound healing Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 26:4445-4457 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Rearrangement of the skin during wound healing depends on plasmin and plasminogen, which serve to degrade fibrin depositions in the provisional matrix and thereby facilitate keratinocyte migration. In the current study, we investigated whether plasmin and plasminogen likewise played a role during the development of skin cancer. To test this, we set up a chemically induced skin tumor model in a cohort of mice and found that skin tumor growth in Plg(-/-) male mice was reduced by 52% compared with wild-type controls. Histological analyses suggested that the growth-restricting effect of plasminogen deficiency was due to thrombosis and lost patency of the tumor vasculature, resulting in tumor necrosis. The connection between plasmin-dependent fibrinolysis, vascular patency, and tumor growth was further substantiated as the effect of plasminogen deficiency on tumor growth could be reverted by superimposing heterozygous fibrinogen deficiency on Plg(-/-) mice. Tumors derived from these Fib(-/+);Plg(-/-) mice displayed a significantly decreased level of tumor thrombosis compared with Plg(-/-) mice. In summary, these data indicate that plasmin-driven fibrinolysis facilitates tumor growth by maintaining patency of the tumor vasculature. |
| Databáze: | OpenAIRE |
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