N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer.
Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial-mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.
Jennbacken
Karin
K
Lundberg Laboratory for Cancer Research, Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gula Stråket 8, SE-413 45 Göteborg, Sweden.
Tesan
Tajana
T
Wang
Wanzhong
W
Gustavsson
Heléne
H
Damber
Jan-Erik
JE
Welén
Karin
K
D000728:Androgens / Q000172:deficiency* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology; D014183:Transplantation, Heterologous; D017211:Treatment Failure; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000728:Androgens; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D011944:Receptors, Androgen