Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.
After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin.
Sehgal
I
I
Department of Biochemistry, Mayo Clinic, Rochester, MN 55905.
Powers
S
S
Huntley
B
B
Powis
G
G
Pittelkow
M
M
Maihle
N J
NJ
D000728:Androgens / Q000378:metabolism*; D002455:Cell Division; D010450:Endopeptidases / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D006133:Growth Substances; D018028:Receptors, Neurotensin; D009496:Neurotensin; D010450:Endopeptidases