In vitro inhibition of human malignant brain tumour cell line proliferation by anti-urokinase-type plasminogen activator monoclonal antibodies

A brain tumour-associated marker, urokinase(UK), was investigated using rab bit anti-UK polyclonal and murine anti-UK monoclonal antibodies, which were prepared by immunization with low molecular weight UK (LMW-UK) and high mo lecular weight urokinase (HMW-UK) synthetic peptide respectively. The polyc lonal antibody cross-reacted with both LMW-UK and HWW-UK, whereas the murin e MAbs were specific for HMW-UK. These immunological probes were used to st udy urokinase in glioma extracts, tissues, sera and cell lines that had bee n prepared from primary cultures of freshly dissected gliomas. Radioimmunoa ssays showed that glioma extracts had much higher level (5- to 44-fold) of UK than normal human brain extracts. This result was confirmed by immunoblo tting of electrophoresis gels of glioma and human brain extracts. Immunohis tochemical study using anti-UK MAb demonstrated much higher levels of UK in glioma tissue than normal brain tissue. Immunohistochemical study using an ti-UK MAbs localized UK on the cell surface of glioma cells. Anti-UK MAbs i nhibited the proliferation of AA cell lines and GB cell lines (50% to > 90% ) and exerted minor effects (less than or equal to 20%) an normal human liv er, intestine and lymphocyte cell lines. Taken together these results sugge st that anti-UK MAbs may have therapeutic potential for human gliomas and c ancer metastasis.