Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.

Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.
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维生素D结合蛋白-巨噬细胞激活因子直接抑制前列腺癌细胞的增殖、迁移和uPAR表达。

DOI:
10.1371/journal.pone.0013428
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发表时间:
2010-10-18
期刊:
影响因子:
3.7
通讯作者:
Fannon, Michael
Fannon, Michael
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gregory, Kalvin J.;Zhao, Bing;Bielenberg, Diane R.;Dridi, Sami;Wu, Jason;Jiang, Weihua;Huang, Bin;Pirie-Shepherd, Steven;Fannon, Michael

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维生素D结合蛋白-巨噬细胞激活因子(DBP-MAF)是一种有效的肿瘤生长抑制因子。然而,它的活性被归因于间接机制,如通过激活巨噬细胞增强免疫反应和抑制肿瘤生长所需的血管生长。在这项研究中,我们首次表明,在没有巨噬细胞的情况下,DBP-MAF对前列腺癌细胞具有直接而有效的作用。DBP-MAF在LNCaP和PC3前列腺癌细胞系以及这些细胞的转移克隆的增殖研究中显示出抑制活性。用膜联蛋白V和碘化丙啶进行的流式细胞术研究表明,这种抑制活性不是由于细胞凋亡或细胞死亡所致。DBP-MAF在体外也具有抑制前列腺癌细胞迁移的能力。最后,DBP-MAF被证明能降低前列腺癌细胞中尿激酶型纤溶酶原激活剂受体(UPAR)的表达。有证据表明,该受体的激活与肿瘤转移有关。这些研究表明,DBP-MAF对前列腺肿瘤细胞具有很强的抑制活性,不依赖于其巨噬细胞的激活。
Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.
DOI: 10.1038/nature08151
发表时间: 2009-07-09
期刊: NATURE
影响因子: 64.8
作者:
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发表时间: 1999-01-01
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DOI: 10.1083/jcb.152.4.777
发表时间: 2001-02-19
期刊: The Journal of cell biology
影响因子: --
作者:
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DOI: 10.1016/0003-2697(86)90131-4
发表时间: 1986-01-01
影响因子: 2.9
作者:
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DOI: 10.1016/s1476-5586(03)80015-5
发表时间: 2003-01-01
期刊: NEOPLASIA
影响因子: 4.8
作者:
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通讯作者: Pirie-Shepherd, S