Many of the alterations in the
insulin-like growth factor (IGF) axis in
prostatic 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
protein 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 completely ascertained. In this study, we analyzed the localization of
IGFBP-rP1 in
prostate cancer and benign prostate tissues using immunohistochemistry and a polyclonal antibody, T1A12, that is specific for
IGFBP-rP1. The most intense staining was observed in nerves, whereas smooth muscle cells in the prostate stained weakly. Lymphocytes were always negative. When normal prostatic secretory epithelium was present, staining was usually absent. The lining secretory epithelium stained positively in 0 of 12 (0%) cases of
benign prostatic hyperplasia, 57 of 63 (90.5%) primary
adenocarcinomas, and 7 of 7 (100%)
prostate cancer metastases.
Prostatic intraepithelial neoplasia showed a similar pattern of staining to that observed for the invasive
tumors. 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-free-
conditioned media from all prostatic cell lines. In contrast to these results,
tumor xenografts generated by direct intraosseous injection of LNCaP or C4-2 to bone marrow space resulted in
tumors that stained positively for
IGFBP-rP1. Our results show that
IGFBP-rP1 is expressed in both in 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.