Expression and localization of placenta growth factor and PlGF receptors in human meningiomas

It has previously been suggested that in human brain tumours, endothelial c ell proliferation during angiogenesis is regulated by a paracrine mechanism involving vascular endothelial growth factor (VEGF) and its receptors (VEG F receptor 1 and VEGF receptor 2). The mechanism of growth factor up-regula tion is based on hypoxic activation of mRNA expression and mRNA stabilizati on and genetic events, leading to an increase of growth factor gene express ion. The role of the other newly discovered VEGF family members with a high specificity for endothelial cells in the pathogenesis of glial neoplasms i s unknown, To investigate which other members of the VEGF family are overex pressed in human brain tumours, the mRNA levels of placenta growth factor ( PIGF), VEGF-A, and VEGF-B genes were determined by northern blot analysis i n surgically obtained human meningiomas. In the 16 meningiomas examined, th e mRNA for PIGF was highly expressed in four tumours and VEGF-A mRNA was hi ghly abundant in three tumour samples. There was no close correlation betwe en PIGF mRNA levels and VEGF-A expression levels. VEGF-B mRNA was abundantl y expressed in all tumour samples at uniform levels. In a PIGF-positive tum our sample, immunoreactive VEGFR-1 and VEGFR-2 were detected in endothelial cells of the blood vessels. PIGF protein was detectable in most bat not al l capillaries of the tumour. PIGF is thus highly up-regulated in a subset o f human meningiomas and may therefore have functions, in some tumour vessel s, connected to endothelial cell maturation and tube formation. These findi ngs suggest that PIGF, in addition to VEGF-A, may be another positive facto r in tumour angiogenesis in human meningiomas. Copyright (C) 1999 John Wile y & Sons, Ltd.