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 c ell surface by expressing urokinase receptors (uPAR) in order to focus the pericellular space plasminogen-dependent proteolysis important in matrix re modeling and cell movement, This study examines the uPAR levels of tumor-as sociated macro phages (TAM) of invasive breast carcinomas, of TAMs from duc tal carcinoma in situ (DCIS) and of macrophages derived from normal (non-tu mor) breast tissue. TAMs from invasive breast carcinomas (n = 30), from DCI S (n = 12), and macrophages from normal breast tissue (n = 30) were culture d and immunocytochemically phenotyped by using a panel of antibodies. Uroki nase receptor levels were determined by Western blot analysis and in cell-f ree supernatants by enzyme-linked immunosorbent assay. Urokinase receptor c ell surface fluorescence intensity was determined by FAGS and by confocal l aser scan microscopy, Urokinase-receptor mRNA was detected by in situ hybri dization, TAMs of invasive breast carcinomas and of DCIS possess significan tly elevated uPAR levels compared,vith macrophages derived front normal bre ast tissue. Conclusions: activated macrophages with elevated uPAR levels be long to inflammatory areas in close vicinity of infiltrating and non-infilt rating,a (DCIS) tumor cells. Blood monocytes that possess elevated uPAR-lev els may be selectively recruited from the bloodstream to inflammatory sites close to carcinoma cells, and/or breast cancer and precursor lesions may i nduce elevated uPAR-levels in TAMs by paracrine interactions.