Urokinase plasminogen activator receptor (CD87) expression of tumor-associated macrophages in ductal carcinoma in situ, breast cancer, and resident macrophages of normal breast tissue.
Macrophages concentrate urokinase-type plasminogen activator (uPA) at the cell surface by expressing urokinase receptors (uPAR) in order to focus the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. This study examines the uPAR levels of tumor-associated macrophages (TAM) of invasive breast carcinomas, of TAMs from ductal carcinoma in situ (DCIS) and of macrophages derived from normal (non-tumor) breast tissue. TAMs from invasive breast carcinomas (n = 30), from DCIS (n = 12), and macrophages from normal breast tissue (n = 30) were cultured and immunocytochemically phenotyped by using a panel of antibodies. Urokinase receptor levels were determined by Western blot analysis and in cell-free supernatants by enzyme-linked immunosorbent assay. Urokinase receptor cell surface fluorescence intensity was determined by FACS and by confocal laser scan microscopy. Urokinase-receptor mRNA was detected by in situ hybridization. TAMs of invasive breast carcinomas and of DCIS possess significantly elevated uPAR levels compared with macrophages derived from normal breast tissue.


CONCLUSIONS
activated macrophages with elevated uPAR levels belong to inflammatory areas in close vicinity of infiltrating and non-infiltrating (DCIS) tumor cells. Blood monocytes that possess elevated uPAR-levels may be selectively recruited from the bloodstream to inflammatory sites close to carcinoma cells, and/or breast cancer and precursor lesions may induce elevated uPAR-levels in TAMs by paracrine interactions.
Department of Pathology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany. ralf.hildenbrand@path.ma.uni-heidelberg.de
R
R
Hildenbrand
G
G
Wolf
B
B
Böhme
U
U
Bleyl
A
A
Steinborn
D001943:Breast Neoplasms / Q000378:metabolism*; D018821:CD18 Antigens / Q000096:biosynthesis; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D005260:Female; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator