Abstract:
:In the bone matrix, insulin-like growth factors (IGFs) are the most abundant growth factors and IGF binding protein 5 (IGFBP-5) is the major IGFBP. Our previous study suggested that IGFs stored in the bone matrix and prostate-specific antigen (PSA) play an important role in prostate cancer (PC) bone metastasis. However, it is not clear how IGF signaling is activated in the bone microenvironment of PC metastasis. Therefore, we investigated whether PSA degrades IGFBP-5 and enhances biological activity of IGF. Enzymatically active PSA degraded the recombinant IGFBP-5 protein in a dose- and time-dependent manner and a serine protease inhibitor suppressed this degradation. Furthermore, PSA induced IGF-mediated type I IGF receptor phosphorylation that was inhibited by coincubation with IGFBP-5. The present study indicates PSA derived from PC cells can enhance IGF bioavailability in the bone microenvironment of PC metastasis, thereby permitting PC survival and malignant progression in the bone microenvironment.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Maeda H,Yonou H,Yano K,Ishii G,Saito S,Ochiai Adoi
10.1016/j.bbrc.2009.01.096subject
Has Abstractpub_date
2009-04-10 00:00:00pages
311-6issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(09)00151-Xjournal_volume
381pub_type
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