Distribution of Nerve Growth Factor-Like Protein and Nerve Growth Factor Receptor in Human Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma

Abstract

Recent observations from our laboratory have identified a nerve growth factor (NGF)-like protein in conditioned media of stromal cells and neoplastic epithelial cells of the human prostate which mediates paracrine interactive growth of both cell types in vitro. In order to investigate the location of this NGF-like protein in the human prostate in vivo, and whether a nerve growth factor receptor (NGF-R) could be identified, we have carried out immunocytochemical studies on frozen tissue sections of human benign prostatic hyperplasia (BPH), prostatic adenocarcinoma and normal prostatic tissue. The NGF-like protein localized predominantly to the stromal component of BPH, adenocarcinoma and normal (non-cancerous) prostatic tissue. Conversely, the NGF-R localized predominantly to the epithelial cells of these tissues. Renal tissue provided negative controls for both the NGF-like protein and the NGF-R. The testis provided positive controls for both the NGF-like protein and the NGF-R. These results provide corroborative evidence for a NGF-like protein produced by stromal cells which interacts with a NGF-R on the adjacent epithelial cells thereby mediating paracrine interactive growth regulation of the human prostate.

Comparison of the effect of oestradiol, tamoxifen and raloxifene on nerve growth factor-alpha expression in specific neonatal mouse uterine cell types using laser capture microdissection

“…The highest level of p75 NTR was found in the myometrium, confirming a previous report (Lommatzsch et al 1999). p75 NTR is involved in the paracrine action of NGF in the prostate (Graham et al 1992) and our results suggest that a similar action could occur in the uterus. With the expression of NGF in the luminal epithelium there is also a possibility of an autocrine loop existing.…”

Neurotrophin receptor p75NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

“…20 The common molecular mechanism for loss of p75 NTR expression in all these cell lines 3 appears to be loss of mRNA stability. 8 Hence, complete expression of the p75 NTR in the normal prostate, partial loss of expression of the p75 NTR in organ-confined adenocarcinoma tissue [3][4][5][6][7] and complete loss of p75 NTR expression in 4 prostate epithelial tumor cell lines derived from metastases 8 is indicative of an inverse association of p75 NTR expression with malignant progression of the human prostate. These observations are consistent with the elimination of a putative p75 NTR tumor suppressor during malignant transformation and progression of the prostate.…”

“…Interestingly, the prostate is the second most abundant source of NGF after the nervous system in man. Whereas the p75 NTR is expressed in normal human prostate epithelial cells, its expression is lost during progression to adenocarcinoma as shown through immunoblot, 3 immunofluorescence, 4 immunohistochemistry 5,6 and Scatchard plot analysis. 5 This progressive loss of p75 NTR expression correlates with increased Gleason's score of organ confined cancer, 7 and its expression is completely absent from 4 naturally occurring human prostate tumor cell lines derived from metastases.…”

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

“…Previous morphological studies suggest that the stroma plays a critical role in affecting the growth and maturation of the prostatic epithelium 27 and that NGF is a secreted protein with its receptors located in the epithelium. 28 We propose that it is the nerves of the prostate that are the origin of NGF which interacts with its receptors in the epithelium, and thereby constitutes a mechanism whereby the autonomic nervous system impacts prostate morphogenesis (manipulation of NGF abundance).…”