Unimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor.
Unimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor.
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DOI：
10.1002/ijc.25326
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Noel, Agnes
中科院分区：
文献类型：
--
作者：
Masset, Anne;Maillard, Catherine;Sounni, Nor Eddine;Jacobs, Nathalie;Bruyere, Francoise;Delvenne, Philippe;Tacke, Marlene;Reinheckel, Thomas;Foidart, Jean-Michel;Coussens, Lisa M.;Noel, Agnes
血管生成、细胞外基质重塑和细胞迁移与癌症进展相关，并且至少涉及纤溶酶原激活系统及其主要生理抑制剂纤溶酶原激活物抑制剂-1（派-1）。考虑到公认的重要性，派-1在调节肿瘤血管生成和侵袭的小鼠皮肤肿瘤移植模型，我们探讨了派-1的功能意义，在肿瘤进展的早期阶段，在多阶段上皮癌变的转基因小鼠模型（K14-HPV 16小鼠）。我们研究了派-1基因缺失对炎症、血管生成、淋巴管生成以及肿瘤进展的影响。在该模型中，派-1缺乏既不损害角质形成细胞过度增殖或肿瘤发展，也不影响炎性细胞的浸润和血管生成或淋巴管生成脉管系统的发展。我们报告的证据，伴随淋巴管和血管生成开关独立派-1状态。总之，这些数据表明，派-1是不是速率限制肿瘤进展和血管化在癌前进展，或派-1和其他肿瘤调节因子之间存在功能冗余，掩盖了派-1缺乏的影响，在这个长期模型的多阶段上皮癌发生。
Angiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the plasminogen activator inhibitor-1 (PAI-1). Considering the recognized importance of PAI-1 in the regulation of tumor angiogenesis and invasion in murine models of skin tumor transplantation, we explored the functional significance of PAI-1 during early stages of neoplastic progression in the transgenic mouse model of multistage epithelial carcinogenesis (K14-HPV16 mice). We have studied the effect of genetic deletion of PAI-1 on inflammation, angiogenesis, lymphangiogenesis, as well as tumor progression. In this model, PAI-1 deficiency neither impaired keratinocyte hyperproliferation or tumor development, nor affected the infiltration of inflammatory cells and development of angiogenic or lymphangiogenic vasculature. We are reporting evidence for concomitant lymphangiogenic and angiogenic switches independent to PAI-1 status. Taken together, these data indicate that PAI-1 is not rate limiting for neoplastic progression and vascularization during premalignant progression, or that there is a functional redundancy between PAI-1 and other tumor regulators, masking the effect of PAI-1 deficiency in this long-term model of multi-stage epithelial carcinogenesis.
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影响因子：
5.4
作者：
ARBEIT, JM;MUNGER, K;HANAHAN, D
通讯作者：
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影响因子：
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作者：
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通讯作者：
Berbary, E