Immunohistochemical localisation of tissue plasminogen activator in human brain tumours

Abstract

Summary The distribution of tissue plasminogen activator (t-PA) has been studied in a series of 38 human brain tumours and two specimens of cerebral cortex, using the monoclonal antibody ESP6. t-PA was localised in vascular endothelium in the majority of tumours and both the cortical specimens, confirmed by double staining with Ulex europaeus lectin (Uel) and Factor 8-related antigen. Nineteen out of 22 high grade astrocytomas showed strong endothelial staining whereas staining was weak or absent in the four low grade astrocytomas studied. No consistent relationship was found between the pattern of staining and tumour grade in the other tumours, although strong staining of the three metastatic lesions with Uel was observed. Among the astroglial tumours only one glioblastoma showed any tumour cell staining for t-PA, which raises questions concerning the origin of t-PA producing cells derived from human gliomas in vitro. Studies of t-PA in brain tumours should take account of this vascular localisation before concluding that the activity is derived from neoplastic cells.

Regulation of in vitro glia‐induced microvessel morphogenesis by urokinase

“…Neuronal homeostasis is likely to be suboptimal in regions of pathological neovascularization, and proliferating endothelial cells must reorganize into microvascular forms as a prerequisite for the higher order endothelial differentiation associated with blood-brain barrier expression (Rosenstein et al, 1992). The sensitivity of morphogenic glial-endothelial interactions to alterations in plasminogen activation may account, in part, for the CNS microvasculopathies associated with neoplasia (Franks and Ellis, 1989;Wolff et al, 1993), diabetes (Grant and Guay, 1991;Maiello et al, 19921, inflammation (Niedbala and Stein, 1991;Murphy and Hart, 19921, and lead toxicity . The pharmacologic manipulation of the plasminogen activation pathway might be used to augment other therapeutic approaches for treating diseases of altered microvessel growth and differentiation within the CNS.…”

Proteases and Their Inhibitors in Gliomas

“…tPA is the less extensively studied in gliomas than uPA. Benign brain tumors have more tPA than malignant tumors 187 but tPA immunoreactivity was more prominent in endothelial cells of high grade than low grade gliomas 188 . The significance of tPA in brain tumors is unknown but it is produced by racine and human gliomas 189,190 .…”

The Role of Hemostatic System Inhibitors in Malignancy

“…[208][209][210][211][212][213] Similarly, high expression of tissue plasminogen activator (t-PA) in cancer tissue implicated poor prognosis. 214,215 Thus, it would be expected that PAI-1, serving as inhibitor of plasminogen activator (PAs), interferes with cancer progression. However, an interesting, albeit paradoxical discovery, that PAI-1 overexpression correlates with unfavorable prognosis, 208,213,214 prompted a revision of our understanding of how the plasminogen system functions in cancer biology.…”