Expression of receptors for luteinizing hormone-releasing hormone (LH-RH) in prostate cancers following therapy with LH-RH agonists.
OBJECTIVE
In addition to their expression on pituitary cells, receptors for luteinizing hormone-releasing hormone (LH-RH) are found on most prostate cancer cells. These tumoral LH-RH receptors mediate the direct cytotoxic effects of LH-RH analogs and are potential therapeutic targets. Although pituitary LH-RH receptors are downregulated following prolonged exposure to LH-RH agonists, there is no evidence that tumoral receptors behave in a similar manner. To better characterize expression of tumoral LH-RH receptors, specimens of prostate cancer from various cohorts of patients were analyzed.


METHODS
Surgical specimens were obtained from untreated patients with prostate cancer and from patients with metastatic castration-resistant prostate cancer previously treated with bilateral orchiectomy. To address the possibility of receptor downregulation, two additional cohorts of patients who had been previously treated with LH-RH agonists were included. One group received neoadjuvant therapy prior to prostatectomy, and the other group was treated for metastatic disease with LH-RH agonists and, at progression, required palliative resection of the prostate. Lymph node metastases from previously untreated patients were subjected to similar analysis.


RESULTS
Expression of LH-RH receptors was found in most specimens. The relative expression of LH-RH receptor mRNA in untreated patients was greater in patients whose tumor had received a Gleason score <8.


CONCLUSIONS
LH-RH receptor expression persisted despite prolonged exposure to LH-RH agonists. These findings support the concept of targeting cytotoxic LH-RH analogs to prostatic LH-RH receptors, using these receptors to gain entry into cancer cells to deliver a hybridized cytotoxic moiety for the treatment of prostate cancer.
Liu
Stephen V
SV
Division of Cancer Medicine and Blood Diseases, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
Schally
Andrew V
AV
Hawes
Debra
D
Xiong
Shigang
S
Fazli
Laden
L
Gleave
Martin
M
Cai
Jie
J
Groshen
Susan
S
Brands
Frank
F
Engel
Juergen
J
Pinski
Jacek
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009919:Orchiectomy; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011966:Receptors, LHRH / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D017211:Treatment Failure
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone