Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1

Many of the alterations in the insulin-like growth factor (IGF) axis in pro static disease have been associated with changes in the insulin-like growth factor binding proteins (IGFBPs), a multigene family of proteins that are thought to mediate the action of IGFs on target tissues, IGFBP-related prot ein 1 (rP1), also known as IGFBP-7 or mac25, is a recently described member of the IGFBP family, the biological function of which has yet to be comple tely ascertained. In this study, we analyzed the localization of IGFBP-rP1 in prostate cancer and benign prostate tissues using immunohistochemistry a nd a polyclonal antibody, T1A12, that is specific for IGFBP-rP1, The most i ntense staining Has observed in nerves, whereas smooth muscle cells in the prostate stained weakly, Lymphocytes were always negative. When normal pros tatic secretory epithelium was present, staining was usually absent. The li ning secretory epithelium stained positively in 0 of 12 (0%) cases of benig n prostatic hyperplasia, 57 of 63 (90.5%) primary adenocarcinomas, and 7 of 7 (100%) prostate cancer metastases, Prostatic intraepithelial neoplasia s howed a similar pattern of staining to that observed for the invasive tumor s. Analysis of Northern blots showed that none of the prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B4, 9069E3, DU145, and PC3) expressed IGFBP-rP1 mRNA, This lack of expression was confirmed by immunohistochemistry of s.c .-generated tumor xenografts of LNCaP and C4-2 and by immunoblot on serum-f ree-conditioned media from all prostatic cell lines. In contrast to these r esults, tumor xenografts generated by direct intraosseous injection of LNCa P or C4-2 to bone marrow space resulted in tumors that stained positively f or IGFBP-rP1, Our results show that IGFBP-rP1 is expressed in both ill situ and invasive prostate neoplasms, but not typically in normal secretory or BPH epithelium; furthermore, the expression of IGFBP-rP1 can be induced in human prostate cancer cell lines in vivo on interaction with an appropriate host environment.