Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

TY - JOUR

T1 - Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

AU - Schnack Nielsen, Boye

AU - Rank, Fritz

AU - Engelholm, Lars H

AU - Holm, Arne

AU - Danø, Keld

AU - Behrendt, Niels

N1 - Copyright 2002 Wiley-Liss, Inc.

PY - 2002/4/10

Y1 - 2002/4/10

N2 - The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor-associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling.

AB - The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor-associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling.

KW - Animals

KW - Antibody Formation

KW - Antigens, CD31

KW - Blotting, Western

KW - Breast

KW - Breast Neoplasms

KW - Carcinoma in Situ

KW - Carcinoma, Ductal, Breast

KW - Cross-Linking Reagents

KW - Female

KW - Fluorescent Antibody Technique

KW - Humans

KW - In Situ Hybridization

KW - Mannose-Binding Lectins

KW - Membrane Glycoproteins

KW - RNA, Messenger

KW - Rabbits

KW - Receptors, Cell Surface

KW - Stromal Cells

KW - Transcription, Genetic

KW - U937 Cells

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 11920633

SN - 0898-6924

VL - 98

SP - 656

EP - 664

JO - International Journal of Cancer. Supplement

JF - International Journal of Cancer. Supplement

IS - 5

ER -