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[Cancer Research 59, 2787-2790, June 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2787-2790, June 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Human Prostate Cancer Expresses the Low Affinity Insulin-like Growth Factor Binding Protein IGFBP-rP11

Armelle Degeorges, Fuan Wang, Henry F. Frierson, Jr., Arun Seth, Leland W. K. Chung and Robert A. Sikes2

Department of Urology, Molecular Urology and Therapeutics Program [A. D., F. W., L. W. K. C., R. A. S.] and Department of Pathology [H. F. F.], University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, and Department of Laboratory Medicine and Pathobiology, MRC Group in Periodontal Physiology and Women’s College Hospital, University of Toronto, Toronto ON M5S 1B2, Canada [A. S.]

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.




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Copyright © 1999 by the American Association for Cancer Research.