1,25-Dihydroxyvitamin D3 decreases human prostate cancer cell adhesion and migration.
1,25-Dihydroxyvitamin D3 decreases human prostate cancer cell adhesion and migration.
复制标题
1,25-二羟基维生素 D3 降低人前列腺癌细胞粘附和迁移。
DOI：
10.1016/s0303-7207(00)00226-4
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发表时间：
2000
影响因子：
4.1
通讯作者：
Feldman,D
中科院分区：
文献类型：
--
作者：
Sung,V;Feldman,D
1，25-二羟基维生素-D3 [1，25（OH）2D 3]是维生素D的活性激素代谢物，通过特异性核受体抑制几种肿瘤细胞类型的增殖并促进其分化，包括LNCaP、DU 145和PC-3前列腺癌细胞系以及原发性前列腺肿瘤细胞系。1，25（OH）_2D_3在体外也能降低乳腺癌和前列腺癌细胞株的侵袭能力。我们在DU 145和PC-3前列腺癌细胞系中证实了后者的发现，并进一步表明1，25（OH）2D 3抑制了整体侵袭、细胞粘附和向基底膜基质蛋白层粘连蛋白的迁移。这些变化似乎部分归因于1，25（OH）2D 3诱导的α6和β4整联蛋白表达减少，这两种蛋白都是层粘连蛋白的受体，并与体外前列腺癌细胞迁移和侵袭的增加有关。用抗体阻断这些特定整联蛋白的功能可抑制细胞的粘附和迁移。总的来说，这些数据表明，1，25（OH）2D 3除了减少肿瘤细胞的增殖外，还可以通过调节选定的细胞表面粘附分子来抑制前列腺癌细胞的侵袭。
1,25-dihydroxyvitamin-D3[1,25(OH)2D3], the active hormonal metabolite of vitamin D, acts through a specific nuclear receptor to inhibit proliferation and promote differentiation of several tumor cell types including the LNCaP, DU145 and PC-3 prostate cancer cell lines as well as primary prostate tumor lines. 1,25(OH)2D3can also decrease invasion of breast and prostate cancer cell lines in vitro. We confirm this latter finding in the DU145 and PC-3 prostate cancer cell lines, and further show that 1,25(OH)2D3inhibits overall invasion, cell adhesion and migration to the basement membrane matrix protein laminin. These changes appear to be due in part to a 1,25(OH)2D3-induced decrease in expression of α6 and β4 integrins, both of which are receptors for laminin and associated with increased migration and invasion of prostate cancer cells in vitro. Blocking function of these particular integrins with antibodies inhibits both adhesion and migration of the cells. Collectively, these data demonstrate that 1,25(OH)2D3, in addition to decreasing proliferation of tumor cells, can also inhibit prostate cancer cell invasion through modulation of select cell surface adhesion molecules.