Kisspeptin is released from human prostate cancer cell lines but plasma kisspeptin is not elevated in patients with prostate cancer

Abstract

Abstract. Kisspeptin, the product of the KiSS-1 gene, inhibits metastasis and stimulates the hypothalamo-pituitarygonadal axis. Kisspeptin is therefore a putative target in the treatment of hormone-sensitive malignancies. Prostatic carcinoma remains a significant cause of mortality despite improvements in therapy. The role of kisspeptin in prostatic carcinoma remains undefined. We therefore aimed to investigate release of kisspeptin by prostatic cancer cell lines; investigate expression of KiSS-1 in human prostate tissue; investigate whether patients with prostate carcinoma have elevated plasma kisspeptin. 1) Culture medium from prostatic carcinoma cell lines LNCaP, DU145 and PC3 was assayed for kisspeptin immunoreactivity (-IR). Kisspeptin-IR release was detectable from all three cell lines. The effect of hydroxyflutamide, gefitinib and resveratrol on kisspeptin-IR release from these cell lines was also investigated. No effect of the drugs tested on release of kisspeptin-IR was observed. 2) Expression of KiSS-1 in human prostate tissue (n=4) was investigated using in situ hybridisation. Expression of KiSS-1 was detected in human prostate tissue. 3) Plasma kisspeptin-IR was compared in 92 patients with prostatic carcinoma and 73 male controls. Kisspeptin-IR was not detected in the plasma of either patients with prostate cancer or control patients. We have therefore shown for the first time the release of kisspeptin-IR by prostatic carcinoma cell lines. We have also shown that KiSS-1 is expressed in human prostate tissue, and that circulating levels of kisspeptin-IR are not elevated in patients with prostatic carcinoma. Further work is required to determine the role of kisspeptin in the prostate.

Expression of Kisspeptin (KISS1) and its Receptor GPR54 (KISS1R) in Prostate Cancer

“…The loss of KISS1 expression correlated with both advanced clinical cancer stages and the loss of KISS1R (23). Interestingly, another study from Curtis et al showed that although kisspeptin is released from human prostate cancer cell lines, plasma kisspeptin levels were not elevated in the examined 92 prostate cancer patients compared to healthy subjects (24). Similarly to the above mentioned data, our present study addressed a significant correlation of KISS1and KISS1R expression with tumor stage and Gleason score of prostate cancer.…”

“…KISS1 and GPR54 are both expressed in various tissues, including the placenta, brain, pituitary, testis, ovary, pancreas, intestine, liver, vascular, thyroid (22). Various functions of KISS1 in normal tissues and in cancer have been recognized (12,23,24). In 2003, for the first time, the major neuroendocrinological role of KISS1-GPR54 system signaling was demonstrated, as being gatekeeper for gonadotropin-releasing hormone (GnRH) release in hypothalamus (25).…”

“…Expression of GPR54 and KISS1 in prostate tissue has not been extensively investigated. Some researchers failed to detect KISS-1 expression in cDNA from human prostate, while several other studies (23,24) were able to demonstrate a definite KISS1 staining in benign prostate tissue. Recent studies have shown a down-regulation of KISS1 expression in prostate cancer, as well as a correlation of clinical stage with KISS1 expression and with expression of KISS1R.…”