To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells.
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.
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.
Crosstalk between androgen-sensitive PCa cells and androgen-insensitive PCa cells might develop the progression of PCa.
Anticancer research. 2018 Apr [Epub]
Yuta Takezawa, Kouji Izumi, Kazuaki Machioka, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Ariunbold Natsagdorj, Yoshifumi Kadono, Evan T Keller, Jian Zhang, Atsushi Mizokami
Integrative Cancer Therapy and Urology, Division of Cancer Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Integrative Cancer Therapy and Urology, Division of Cancer Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan .