Elevated level of inhibin-alpha subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer.
The biological function of inhibin-alpha subunit (INH alpha) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INH alpha in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INH alpha. We conducted a cross-sectional study to determine a link between INH alpha expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INH alpha in advanced cancer. Elevated expression of INH alpha in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INH alpha in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INH alpha-positive LNCaP demonstrated reduced tumour growth whereas INH alpha-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INH alpha associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INH alpha expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa.
Centre for Urological Research, Monash Institute of Medical Research, Monash University, Melbourne, Victoria 3168, Australia. preetika.balanathan@med.monash.edu.au
P
P
Balanathan
E D
ED
Williams
H
H
Wang
J S
JS
Pedersen
L G
LG
Horvath
M G
MG
Achen
S A
SA
Stacker
G P
GP
Risbridger
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
C094377:inhibin-alpha subunit; D007265:Inhibins