Differential effects of transforming growth factor beta on human prostate cancer cells in vitro.
Transforming growth factor beta (TGF beta) exerts a wide spectrum of activity on many different cell types. Since TGF beta inhibits the growth of a variety of epithelial tumor cells in vitro, we examined the effects of TGF beta on the human prostate cancer cell lines DU145, PC3 and LNCaP for possible inhibitory activity. Growth in monolayer was initially inhibited in a dose-response fashion in the two androgen-independent cell lines, PC3 and DU145 but not in the androgen-dependent LNCaP cells. The rate of growth of the PC3 and DU145 cells treated with TGF beta, however, eventually returned to control levels despite retreatment with TGF beta. Anchorage-independent growth was inhibited to 55% and 16% control levels in PC3 and DU145, respectively. Scatchard analysis showed 1500 and 2900 TGF beta binding sites/cell on DU145 and PC3 cells with Kd = 6.9 and 12 x 10(-12) M, respectively. High-affinity binding could not be demonstrated on LNCaP cells. We also explored the possibility that TGF beta was secreted by these cells. Analysis of conditioned media by immunoprecipitation and a radioreceptor assay showed secretion of TGF beta into the media by DU145 and PC3 but not by LNCaP. Northern analysis showed the presence of TGF beta mRNA in DU145 and PC3, but not in LNCaP. These data indicate that TGF beta might serve as an autocrine inhibitory factor in prostate cancer. In addition, because TGF beta affects a wide range of cell types, TGF beta production by prostate cancer cells may contribute an important paracrine function in the development of tumor stromal tissue and metastases.
Wilding
G
G
Breast Cancer Section, National Cancer Institute, Bethesda, MD.
Zugmeier
G
G
Knabbe
C
C
Flanders
K
K
Gelmann
E
E
D000728:Androgens / Q000494:pharmacology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis / Q000494:pharmacology; D018125:Receptors, Transforming Growth Factor beta; D013936:Thymidine / Q000493:pharmacokinetics; D014158:Transcription, Genetic / Q000187:drug effects; D015291:Transforming Growth Factors / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000728:Androgens; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D013936:Thymidine