Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions

D R Thickett, L Armstrong, A B Millar, D R Thickett, L Armstrong, A B Millar

Abstract

Background: Investigation and management of pleural effusions is an important clinical problem yet the pathogenesis of pleural fluid accumulation is poorly understood. Vascular endothelial growth factor (VEGF) is a potent inducer of capillary permeability that is produced by both malignant and inflammatory cells. A study was undertaken to determine whether VEGF has a potential pathogenic role in the development of pleural effusions and whether VEGF receptors are present on human pleural mesothelial cells.

Methods: Normal and inflamed pleura were examined immunohistochemically for the presence of FLT-1 (the fms-like tyrosine kinase receptor of VEGF). VEGF levels were measured by ELISA in 78 consecutive patients presenting with undiagnosed unilateral pleural effusions and the levels were correlated with the aetiology of the effusions.

Results: Immunohistochemical staining of normal and diseased pleura demonstrated the presence of the FLT-1 VEGF receptor on human mesothelial cells. Median VEGF levels were 2500 pg/ml in the malignant group and 305 pg/ml in the non-malignant group (median difference 1397.5 pg/ml (95% CI 851 to 2693), p<0.005). Median VEGF levels varied according to tumour histology. VEGF levels were also significantly raised compared with transudates (median 36.5 pg/ml) in empyema (4651 pg/ml (95% CI 833 to 10 000), p<0.001) and parainfectious effusions (360 pg/ml (95% CI 46 to 597), p<0.005).

Conclusions: This first report of VEGF receptors on pleural mesothelial cells has indicated a potential mechanism for the biological activity of VEGF on pleural tissue. VEGF levels are raised in the majority of exudative effusions, implying a pathogenic role for this molecule in the development of pleural effusions.

References

    1. Chest. 1993 Nov;104(5):1486-9
    1. Cancer Res. 1993 Jun 15;53(12):2912-8
    1. Anticancer Res. 1996 Jan-Feb;16(1):213-7
    1. Int J Cancer. 1997 Feb 20;74(1):64-8
    1. Mol Biol Cell. 1992 Feb;3(2):211-20
    1. Cancer Res. 1995 Jan 15;55(2):360-8
    1. Development. 1992 Feb;114(2):521-32
    1. J Exp Med. 1994 Jul 1;180(1):341-6
    1. Am J Pathol. 1995 May;146(5):1029-39
    1. Anticancer Res. 1997 Jul-Aug;17(4A):2811-4
    1. Microvasc Res. 1996 May;51(3):347-64
    1. Angiogenesis. 1998;2(1):9-20
    1. Am J Physiol. 1997 Dec;273(6 Pt 2):H2565-74
    1. J Leukoc Biol. 1997 Sep;62(3):397-400
    1. Blood. 1997 Nov 15;90(10):4153-61
    1. Clin Immunol Immunopathol. 1995 Oct;77(1):27-32
    1. Eur Respir J. 1997 Aug;10(8):1701-2
    1. Eur Respir J. 1997 May;10(5):1173-80

Source: PubMed

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