Summary
The plasminogen activation system is a delicately balanced assembly of enzymes which
seems to have primary influence on tumour progression. The conversion of plasminogen
into serine protease plasmin with fibrinolytic activity depends on the actual balance
between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their
inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose
of this study was to determine the exact histological localization of all the major
factors involved in plasminogen activation, and activation inhibition (plasmin system)
in benign and malignant breast tumour samples. Our results show that factors of the
plasmin system are present both in benign and malignant tumours. Cancer cells strongly
labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were
also stained for plasminogen activators at least as intensively as tumour cells in
cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAM.
Staining became sporadic in malignant tumours, cells located at the periphery of tumour
cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples
the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells,
showing characteristics of fibroblasts; but their number was strongly decreased in
the stroma of malignant tumours. These findings indicate that the higher level of
u-PA antigen, detected in malignant breast tumour samples by biochemical techniques,
does not necessarily indicate increased u-PA production by tumour cells but it might
be owing to the increased number of cells producing u-PA as well. In malignant tumours
PAI-1 seems to be decreased in the frontage of malignant cell invasion; i.e. malignant
cells at the host/tumour interface do not express PAI-1 in morphologically detectable
quantity and in the peritumoural connective tissue the number of fibroblasts containing
PAI-1 is also decreased.
