Tumoral and choroidal vascularization:: Differential cellular mechanisms involving plasminogen activator inhibitor type 1
Tumoral and choroidal vascularization:: Differential cellular mechanisms involving plasminogen activator inhibitor type 1
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DOI：
10.2353/ajpath.2007.070074
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发表时间：
2007-10-01
影响因子：
6
通讯作者：
Noel, Agnbs
中科院分区：
文献类型：
--
作者：
Jost, Maud;Maillard, Catherine;Noel, Agnbs
丝氨酸蛋白酶和纤溶酶原激活物抑制剂-1（派-1）之间的适当平衡对于病理性血管生成至关重要。小鼠中派-1缺乏与受损的脉络膜新生血管形成（CNV）和肿瘤血管生成相关。在目前的工作中，我们证明了出乎意料的差异，在这两个过程中的派-1调节的骨髓（BM）来源的细胞的贡献。派-1（-/-）小鼠移植来自野生型小鼠的BM能够支持激光诱导的CNV形成，但不能支持皮肤癌血管化。用派-1 BM移植照射的野生型小鼠防止CNV形成，证明了由BM衍生的细胞递送的派-1的关键作用。相比之下，在派-1缺陷小鼠中，局部派-1产生宿主细胞而不是BM细胞对肿瘤移植物的瞬时浸润足以挽救肿瘤生长和血管生成。这些数据将派-1鉴定为肿瘤血管生成的局部容许土壤的分子决定因子。总之，本研究表明，不同的细胞机制有助于派-1调节肿瘤和CNV。派-1有助于BM依赖性脉络膜血管形成和BM非依赖性肿瘤生长和血管生成。
An adequate balance between serine proteases and their plasminogen activator hihibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1(-/-) mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wildtype mice with PAI-1 BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis; in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis.