Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer

Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix , and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is h ighly expressed by myofibroblasts surrounding invasively growing cancer cel ls. However, the localization of uPA protein has not been settled in the pu blished literature, Because uPA is a secreted molecule, it could conceivabl y be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal car cinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts a nd macrophages in all cases examined. Additionally, in approximately half o f the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 case s, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cel ls, which thus play a major role in generation of proteolytic activity in d uctal breast cancer.