Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization differs from IGFBP-5 protein localization.
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the actions of IGF. We have previously reported that IGFBP-2 messenger ribonucleic acid (mRNA) and protein are increased, and IGFBP-3 protein decreased in malignant prostate epithelium compared to benign epithelium. In this study, we examined the other IGFBPs secreted by prostate cells in vitro, namely IGFBP-4, -5, and 6. Immunoreactivity and mRNA signals for IGFBP-4 and -6 were localized to epithelial cells, with less signal in stroma. IGFBP-4 immunostaining and hybridization signal were significantly increased in prostate adenocarcinoma compared to those in benign epithelium. Immunostaining for IGFBP-5 was localized to the epithelium and stroma. IGFBP-5 immunoreactivity was significantly increased in malignant compared to benign epithelium. IGFBP-5 mRNA signal was not localized to epithelial cells; rather, the signal was over stromal cells surrounding the acinar structures. These cells are thought to be fibroblasts. We show that IGFBP-4 mRNA and protein and IGFBP-5 protein are increased in malignant epithelium compared to benign epithelium, that IGFBP-6 is present in benign and malignant epithelium, and that there is differential localization of IGFBP-5 mRNA and protein in prostate tissue. IGFBP-5 that is made by fibroblasts appears to be sequestered by epithelial cells. IGFBP-5 may, therefore, be a factor in cellular interactions between stromal and epithelial cells that are of fundamental importance for normal prostatic development and function.
Tennant
M K
MK
Geriatric Research Education and Clinic Center, Veterans Affairs Medical Center, Seattle, Washington 98108, USA.
Thrasher
J B
JB
Twomey
P A
PA
Birnbaum
R S
RS
Plymate
S R
SR
D000368:Aged; D004848:Epithelium / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000032:analysis*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000032:analysis* / Q000235:genetics; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000032:analysis*; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*
D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D007633:Keratins