Granulocyte, granulocyte-macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells.

Granulocyte, granulocyte-macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells.
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DOI:
10.1038/sj.bjc.6690009
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发表时间:
1999-01
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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我们和其他研究人员先前发现集落刺激因子(csf),一般包括粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和巨噬细胞集落刺激因子(M-CSF),促进肺癌细胞的侵袭。在本研究中,我们研究了这些csf对人肺癌细胞明胶酶生成、尿激酶纤溶酶原激活物(uPA)生成及其活性的影响。从人肺腺癌细胞中提取的条件培养基明胶酶谱图显示明胶酶活性在68和92 kDa处有两条主要条带,分别为基质金属蛋白酶(MMP)-2和MMP-9。csf处理增加了68- kda和92-kDa活性,并将一些92-kDa前酶转化为82-kDa酶,这与MMP-9的活性形式一致。来自癌细胞的条件培养基的纤溶酶原激活物酶谱图显示,CSF治疗导致48-55 kDa的纤溶酶原依赖性明胶溶解活性增加,其特征为人类uPA。用csf处理的癌细胞的条件培养基刺激了纤溶酶原向纤溶酶的转化,直接证明了增强的uPA增加纤溶酶依赖性蛋白水解的能力。csf刺激癌细胞的侵袭行为增强与MMPs和uPA活性的增加密切相关。这些数据表明,肿瘤细胞对脑脊液治疗的反应增强了细胞外基质降解蛋白酶的产生,可能代表了一种促进癌细胞侵袭行为的生化机制。©1999癌症研究运动
We and other researchers have previously found that colony-stimulating factors (CSFs), which generally include granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), promote invasion by lung cancer cells. In the present study, we studied the effects of these CSFs on gelatinase production, urokinase plasminogen activator (uPA) production and their activity in human lung cancer cells. Gelatin zymographs of conditioned media derived from human lung adenocarcinoma cell lines revealed two major bands of gelatinase activity at 68 and 92 kDa, which were characterized as matrix metalloproteinase (MMP)-2 and MMP-9 respectively. Treatment with CSFs increased the 68- and 92-kDa activity and converted some of a 92-kDa proenzyme to an 82-kDa enzyme that was consistent with an active form of the MMP-9. Plasminogen activator zymographs of the conditioned media from the cancer cells showed that CSF treatment resulted in an increase in a 48–55 kDa plasminogen-dependent gelatinolytic activity that was characterized as human uPA. The conditioned medium from the cancer cells treated with CSFs stimulated the conversion of plasminogen to plasmin, providing a direct demonstration of the ability of enhanced uPA to increase plasmin-dependent proteolysis. The enhanced invasive behaviour of the cancer cells stimulated by CSFs was well correlated with the increase in MMPs and uPA activities. These data suggest that the enhanced production of extracellular matrix-degrading proteinases by the cancer cells in response to CSF treatment may represent a biochemical mechanism which promotes the invasive behaviour of the cancer cells. © 1999 Cancer Research Campaign
DOI: 10.1007/bf00123394
发表时间: 1996-09-01
影响因子: 4
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期刊: BIOCHIMICA ET BIOPHYSICA ACTA
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通讯作者: THOMASSEN, MJ
DOI: 10.1002/j.1460-2075.1990.tb08213.x
发表时间: 1990-04-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
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通讯作者: BLASI, F