[Androgen regulation of secreted growth factors in prostate carcinoma cell and tumor lines].
Previous studies have shown that part of steroid hormone action on hormone dependent carcinoma cells is mediated through secreted autocrine and paracrine growth factors. Coculture experiments using the androgen receptor positive human prostate carcinoma cell line LNCaP as feeder cells and the androgen receptor negative prostate cell line DU 145 as indicator cells, such as experiments with conditioned medium suggest that androgens might regulate proliferation of prostate carcinoma through a similar mechanism. LNCaP and DU 145 cells express high affinity EGF-receptors and show an increased growth rate under treatment with EGF, TGF alpha and FGF. The growth stimulating potential of LNCaP-conditioned medium can be enhanced by androgens. The polyanionic compounds suramin and dextran sulfates which have been shown to inactivate a variety of growth factors e.g. EGF/TGF alpha inhibit growth of LNCaP cells and DU 145 cells in a dose dependent and reversible fashion. Growth stimulation of LNCaP cells by EGF/TGF alpha can be completely reversed by simultaneous addition of polyanions but they inhibit androgen stimulation only partially. These data suggest the existence of at least two different mechanisms of growth regulation by androgens which can be distinguished by their different sensitivity of prostatic carcinoma cells to growth factor inhibitory agents. In order to investigate the therapeutic potential of these substances in complex, heterogeneous cell systems of solid tumors we treated 8 representative human prostate cancer lines in the nude mouse model. Systemic applications of polyanions revealed significant growth inhibition in hormone dependent as well as hormone independent xenografts. In androgen responsive lines growth inhibition was intensified by additional androgen withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Kellner
U
U
Abteilung für Klinische Chemie, II. Medizinische Klinik, Universitätskrankenhaus Hamburg-Eppendorf.
Wagner
B
B
Otto
U
U
Voigt
K D
KD
Dietel
M
M
Knabbe
C
C
D000728:Androgens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors