Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1.
Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1.
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发表时间：
2000-10
期刊：
影响因子：
11.2
通讯作者：
L. Gutierrez;A. Schulman;Teresa Brito-Robinson;F. Noria;V. Ploplis;F. Castellino
中科院分区：
文献类型：
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作者：
L. Gutierrez;A. Schulman;Teresa Brito-Robinson;F. Noria;V. Ploplis;F. Castellino
使用纤维肉瘤肿瘤模型研究了尿激酶型纤溶酶原激活物（UPA-/-）及其抑制剂纤溶酶原激活物抑制剂-1（派-1-/-）靶向缺陷小鼠体内肿瘤进展。将鼠T241纤维肉瘤细胞s.c.植入具有以下基因型的三组小鼠中：野生型（WT）、UPA-/-和派-1-/-。相对于WT小鼠，UPA-/-和派-1-/-小鼠的原发性肿瘤生长显著减少。与WT小鼠相比，UPA-/-和派-1-/-小鼠的肿瘤显示出较低的增殖指数和较高的凋亡指数，并显示出不同的新生血管形态。这些结果与这些基因缺失小鼠中该肿瘤的生长速率降低一致。肿瘤的免疫组织化学分析显示，血管和血管内皮生长因子的表达减少，只有在派-1-/-小鼠的肿瘤。在这些相同的动物中，由碱性成纤维细胞生长因子诱导的角膜血管生成的相对程度的分析证实了派-1-/-小鼠对新血管形成的抗性。结果表明，宿主纤溶系统在该模型中的肿瘤生长中起着重要作用。宿主表达该系统组分的改变可能通过影响肿瘤细胞死亡和增殖之间的平衡以及侵袭性和血管生成所需的细胞外基质变化来改变肿瘤生长和传播。
In vivo tumor progression in mice with targeted deficiencies in urokinase-type plasminogen activator (UPA-/-) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1-/-), was studied using a fibrosarcoma tumor model. Murine T241 fibrosarcoma cells were s.c. implanted into three groups of mice with the following genotypes, wild-type (WT), UPA-/-, and PAI-1-/-. A significantly diminished primary tumor growth in UPA-/- and PAI-1-/- mice occurred, relative to WT mice. Tumors in UPA-/- and PAI-1-/- mice displayed lower proliferative and higher apoptotic indices and displayed a different neovascular morphology, as compared with WT mice. These results are consistent with the decreased growth rates of this tumor in these gene-deleted mice. Immunohistochemical analyses of the tumors revealed a decrease in vascularity and vascular endothelial growth factor expression only in tumors in PAI-1-/- mice. Analyses of the relative extents of corneal angiogenesis in these same animals, induced by basic fibroblast growth factor, corroborated the resistance of PAI-1-/- mice to neovascularization. The results obtained suggest that the host fibrinolytic system plays an important role in tumor growth in this model. Alterations in host expression of components of this system may alter tumor growth and dissemination by affecting the balance between tumor cell death and proliferation, as well as extracellular matrix changes needed for invasiveness and angiogenesis.