Urokinase and macrophages in tumour angiogenesis.

Urokinase and macrophages in tumour angiogenesis.
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肿瘤血管生成中的尿激酶和巨噬细胞。

DOI:
10.1038/bjc.1995.419
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发表时间:
1995-10
影响因子:
8.8
通讯作者:
Stutte, H. J.
Stutte, H. J.
中科院分区:
医学1区
文献类型:
--
作者:
Hildenbrand, R.;Dilger, I.;Hoerlin, A.;Stutte, H. J.

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最近的研究表明,乳腺癌中尿激酶纤溶酶原激活剂 (uPA) 和纤溶酶原激活剂抑制剂 1 (PAI-1) 水平升高与无复发生存时间缩短和总生存时间缩短的风险增加相关。尿激酶PA和PAI-1是乳腺癌的独立预后指标。纤溶酶原激活剂对于微血管细胞的管形成是不可或缺的,并且它们可以在体外诱导血管生成,这一事实强烈表明uPA和PAI-1在肿瘤新生血管形成中的作用。由于巨噬细胞和肿瘤细胞产生uPA,我们假设肿瘤细胞和肿瘤相关巨噬细胞在血管生成中密切合作。为了研究肿瘤组织中的 uPA 水平和巨噬细胞计数如何与血管生成相关,我们对 42 个原发性浸润性乳腺癌中的微血管进行了计数并测定了 uPA 水平和巨噬细胞含量。使用光学显微镜,我们通过免疫细胞化学染色内皮细胞的 CD31 和因子 VIII 以及巨噬细胞的 CD68 来突出显示血管。获得肿瘤组织提取物后,我们通过 ELISA 测定 uPA 和 PAI-1 水平。发现微血管密度、血管侵犯、uPA水平、巨噬细胞含量和增殖率呈正相关。
Recent studies have shown that elevated levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in breast cancer correlate with an increased risk of a reduced relapse-free survival time and shortened overall survival times. Urokinase PA and PAI-1 are independent prognostic indicators for breast cancer. The fact that plasminogen activators are indispensable for tube formation of microvascular cells and that they may induce angiogenesis in vitro strongly suggests a role for uPA and PAI-1 in tumour neovascularisation. Because macrophages and tumour cells produce uPA, we postulate a close collaboration between tumour cells and tumour-associated macrophages in angiogenesis. To investigate how uPA levels and macrophage counts in tumour tissue correlate with angiogenesis, we counted microvessels and determined uPA levels and macrophage content in 42 primary invasive breast carcinomas. Using light microscopy, we highlighted the vessels by staining their endothelium cells immunocytochemically for CD31 and factor VIII and the macrophages for CD68. After obtaining tumour tissue extracts, we determined the uPA and PAI-1 levels by ELISA. A positive correlation between microvessel density, vascular invasion, uPA level, macrophage content and proliferation rate was found.
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发表时间: 1988-01-01
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影响因子: --
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