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Correlation of VEGF production with IL1 and IL6 secretion by human pituitary adenoma cells

¹ Hormone and Vascular Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK, ² Department of Pathology, University of Otago, Otago, New Zealand, ³ Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield S10 2RX, UK, ⁴ Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Gawber Road, Barnsley S75 2EP, UK

(Correspondence should be addressed to Dr T H Jones; Email: hugh.jones{at}bdgh-tr.trent.nhs.uk)

Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion.

Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1 and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging.

Results: VEGF was detected in conditioned medium of HP75 cells (900±52 pg/ml) and in 82% of tumours tested (range 26–16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P = 0.056; VEGF, P < 0.001 (P values based on Spearman’s test)) and IL1 produced (volume, P < 0.005; VEGF, P < 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1, but not IL6, significantly increased VEGF production.

Conclusions: The significant associations between VEGF and the levels of IL6 and IL1 suggest an important role for these cytokines in the development of these tumours.

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