Effects of adipocytes on the proliferation and differentiation of prostate cancer cells in a 3-D culture model

Effects of adipocytes on the proliferation and differentiation of prostate cancer cells in a 3-D culture model
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DOI:
10.1111/j.1442-2042.2010.02472.x
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发表时间:
2010-04-01
影响因子:
2.6
通讯作者:
Uozumi, Jiro
Uozumi, Jiro
中科院分区:
医学3区
文献类型:
--
作者:
Kaneko, Arata;Satoh, Yuji;Uozumi, Jiro

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目的:探讨脂肪细胞-前列腺癌细胞相互作用影响前列腺癌细胞增殖分化的机制。方法:使用雄性Wistar大鼠的雄激素依赖性细胞系(LNCaP),两个雄激素非依赖性细胞系(PC-3, DU145)和成熟脂肪细胞。癌细胞与分离的成熟脂肪细胞在三维胶原凝胶基质中共培养。观察前列腺癌细胞的形态和增殖能力。对于磷脂酰肌醇3-激酶(PI3K)通路的激活,采用免疫组化方法检测10号染色体上缺失的磷酸酶和紧张素同源物(PTEN)、Akt和Bad的表达。结果:LNCaP细胞与脂肪细胞共培养形成的细胞簇比对照组大。PC-3细胞与脂肪细胞共培养后,未形成较大的细胞团,形成球形和梭形细胞。与对照组相比,共培养组PC-3细胞中Akt的磷酸化水平更高,而LNCaP和DU145细胞中Akt的磷酸化水平无显著差异。结论:脂肪细胞可调节前列腺癌细胞的增殖和分化。PI3K通路的激活可能参与了前列腺癌细胞与脂肪细胞的相互作用。
Objective:To investigate how the mechanism of adipocyte-prostate cancer cell interaction affects the proliferation and differentiation of prostate cancer cells.Methods:An androgen-dependent cell line (LNCaP), two androgen-independent cell lines (PC-3, DU145), and mature adipocytes harvested from male Wistar rats were used. Cancer cells were co-cultured with the isolated mature adipocytes in 3-D collagen gel matrix culture. The morphology and proliferative ability of the prostate cancer cells were examined. With regard to the activation of the phosphatidylinositol 3-kinase (PI3K) pathway, the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN), Akt and Bad were determined by immunohistochemistry.Results:LNCaP cells co-cultured with adipocytes formed larger clusters than those of the control. PC-3 cells co-cultured with adipocytes did not form larger clusters, but formed spherical and spindle-shaped cells. The phosphorylation of Akt in PC-3 cells was greater in the co-cultured group compared with the controls, but there were no significant differences in the phosphorylation of Akt with regard to LNCaP and DU145 cells.Conclusions:Adipocytes could modulate the proliferation and differentiation of prostate cancer cell lines. Activation of the PI3K pathway might be involved in the prostate cancer cell-adipocyte interaction.