Crosstalk Between Androgen-sensitive and Androgen-insensitive Prostate Cancer Cells.

Crosstalk Between Androgen-sensitive and Androgen-insensitive Prostate Cancer Cells.
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DOI:
10.21873/anticanres.12444
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发表时间:
2018-04
影响因子:
2
通讯作者:
Yuta Takezawa;K. Izumi;Kazuaki Machioka;H. Iwamoto;R. Naito;Tomoyuki Makino;S. Kadomoto;Ariunbold Natsagdorj;Y. Kadono;E. Keller;Jian Zhang;A. Mizokami
Yuta Takezawa;K. Izumi;Kazuaki Machioka;H. Iwamoto;R. Naito;Tomoyuki Makino;S. Kadomoto;Ariunbold Natsagdorj;Y. Kadono;E. Keller;Jian Zhang;A. Mizokami
中科院分区:
医学4区
文献类型:
--
作者:
Yuta Takezawa;K. Izumi;Kazuaki Machioka;H. Iwamoto;R. Naito;Tomoyuki Makino;S. Kadomoto;Ariunbold Natsagdorj;Y. Kadono;E. Keller;Jian Zhang;A. Mizokami

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目的探讨雄激素敏感的LNCaP细胞与雄激素不敏感的DU145或PC-3细胞间的串扰。材料与方法将LNCaP细胞与DU145或PC-3细胞共培养,计数LNCaP细胞的数量。在DU145或PC-3细胞存在的情况下,用PSA启动子驱动的荧光素酶报告基因转染LNCaP细胞,用荧光素酶报告基因法检测雄激素受体(AR)活性。采用液相色谱-质谱法(LC-MS/MS)测定培养基中雄激素的浓度。在LNCaP细胞存在的情况下,采用2层腔室研究PC-3和DU145细胞的迁移和侵袭能力。结果LNCaP细胞与DU145细胞共培养,脱氢表雄酮(DHEA)转化为双氢睾酮(DHT),刺激LNCaP细胞增殖和PSA启动子活性。DHT处理后LNCaP细胞的细胞增殖率和AR活性均有所提高,与DU145细胞共培养进一步增强。LNCaP细胞也通过分泌可溶性因子刺激DU145和PC-3细胞的增殖。最后,LNCaP细胞在共培养系统中促进PC-3细胞的迁移和侵袭;但能抑制DU145细胞的迁移和侵袭。结论雄激素敏感型前列腺癌细胞与雄激素不敏感型前列腺癌细胞间的串扰可能促进前列腺癌的进展。
AIM To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells. MATERIALS AND METHODS The numbers of LNCaP cells were counted when co-cultured with DU145 or PC-3 cells and vise versa. Androgen receptor (AR) activity in LNCaP cells was examined by luciferase reporter assay after transfection with a luciferase reporter driven by PSA promoter in the presence of DU145 or PC-3 cells. Concentration of androgens in the medium was measured by liquid chromatography-mass spectrometry (LC-MS/MS). The ability of migration and invasion of PC-3 and DU145 cells was investigated using a 2-layer chamber, in the presence of LNCaP cells. RESULTS Co-culture of LNCaP cells with DU145 cells resulted in the conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT), which stimulated cell proliferation and PSA promoter activity in LNCaP cells. The increased cell proliferation rate and AR activity, induced in LNCaP cells after DHT treatment, was further enhanced by co-culture with DU145 cells. LNCaP cells also stimulated the proliferation of DU145 and PC-3 cells, via secreting soluble factors. Finally, LNCaP cells promoted migration and invasion of PC-3 cells, in a co-culture system; however inhibited migration and invasion of DU145 cells. CONCLUSION Crosstalk between androgen-sensitive PCa cells and androgen-insensitive PCa cells might develop the progression of PCa.