A novel androgen-dependent prostate cancer xenograft model derived from skin metastasis of a Japanese patient.
BACKGROUND
The incidence of, and mortality from, prostate cancer (PCa) has increased in Asian countries over the past decades, partly due to a change in dietary habits. Recent reports have revealed differences in the molecular basis of PCa among people of differing racial or ethnic backgrounds. PCa xenograft models established from Asian patients would be useful for understanding the basis of PCa in Asian populations; we therefore established and characterized a novel PCa xenograft model, JDCaP, from a metastatic skin lesion of a Japanese hormone-refractory prostate cancer (HRPC) patient.


METHODS
Skin metastatic tissue derived from poorly differentiated prostatic adenocarcinoma in a 61-year-old Japanese male was transplanted to nude mice and JDCaP was established by serial passage. Expression of androgen receptor (AR) and prostate-specific antigen (PSA) was evaluated by immunohistochemistry and the AR sequence was analyzed. Hormone sensitivity of JDCaP was investigated in vivo by orchiectomy followed by administration of steroid hormones, including testosterone, estradiol, progesterone, and hydrocortisone. Therapeutic effects of leuprorelin acetate, bicalutamide, flutamide, diethylstilbestrol (DES), and estradiol were investigated.


RESULTS
JDCaP expressed wild-type AR and PSA and showed androgen dependence. Only testosterone administration maintained tumor proliferation after orchiectomy. Administration of leuprorelin acetate, bicalutamide, and flutamide inhibited tumor growth. DES and estradiol also demonstrated significant antitumor effects.


CONCLUSIONS
JDCaP expresses wild-type ARs and exhibits androgen dependence despite its origin from a HRPC patient. The model may be useful to elucidate the molecular basis of PCa in Asian populations and to develop prevention and therapeutic strategies.
Kimura
Takahiro
T
Department of Urology, Jikei University School of Medicine, Tokyo, Japan. tkimura@jikei.ac.jp
Kiyota
Hiroshi
H
Nakata
Daisuke
D
Masaki
Tsuneo
T
Kusaka
Masami
M
Egawa
Shin
S
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D044466:Asian People; D004054:Diethylstilbestrol / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary*; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; C479341:prostate cancer antigen 3, human; D004054:Diethylstilbestrol; D016729:Leuprolide