Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: detection of a non-endothelial function of VEGF in pituitary tumours

Onofri, Chiara; Theodoropoulou, Marily; Losa, Marco; Uhl, Eberhard; Lange, Manfred; Arzt, Eduardo; Stalla, Günter; Renner, Ulrich

doi:10.1677/joe.1.06992

Cited by 62 publications

(59 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As we have previously shown, VEGFA affects not only vascular function and growth in pituitary adenomas but also stimulates proliferation of pituitary tumour cells (Onofri et al 2006). These effects are mediated through differently localised VEGFA receptors, whereby the VEGFR1 is predominantly expressed on tumour cells and the VEGFR2 is exclusively located in endothelial cells (Onofri et al 2006).…”

Section: Discussionmentioning

confidence: 86%

“…These effects are mediated through differently localised VEGFA receptors, whereby the VEGFR1 is predominantly expressed on tumour cells and the VEGFR2 is exclusively located in endothelial cells (Onofri et al 2006). Thus, through the inhibition of VEGFA, curcumin would not only impair the vascularisation of pituitary adenomas but would also suppress the growth stimulatory effects of VEGFA on pituitary tumours.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

Shan

Schaaf

Schmidt³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plantCurcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl2treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

Shan

Schaaf

Schmidt³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The extremely dense vascular network within the anterior pituitary is needed for the rapid release or suppression of pituitary hormones induced by blood-delivered stimulators or inhibitors respectively. The maintenance of the intrapituitary blood vessel system and the microvessel permeability seems to be regulated by VEGF-A derived by FS cells, which represent the major source of this factor in the normal pituitary (Vidal et al 2001, Onofri et al 2006. Inside pituitary adenomas FS cells are rare and the tumour cells produce VEGF-A by themselves (Vidal et al 2001, Onofri et al 2006.…”

Section: Discussionmentioning

confidence: 99%

“…As in many kinds of tumours, neovascularisation through angiogenesis is essential for pituitary adenoma expansion (Turner et al 2000, Onofri et al 2006. Since pituitary tumours grow very slowly in most cases, the vessel density of pituitary adenomas is mostly lower than that of the densely vascularised normal pituitary (Vidal et al 2001, Onofri et al 2006).…”

mentioning

confidence: 99%

“…Since pituitary tumours grow very slowly in most cases, the vessel density of pituitary adenomas is mostly lower than that of the densely vascularised normal pituitary (Vidal et al 2001, Onofri et al 2006). However, VEGF-A is slightly overexpressed in the majority of pituitary adenomas and interestingly, VEGF-A is acting not only as an angiogenic but also as a growth factor on pituitary adenomas through differently expressed VEGF-A receptors in tumour and vessel cells of pituitary adenomas (Onofri et al 2006).…”

mentioning

confidence: 99%

See 1 more Smart Citation

RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells

Shan¹,

Gerez²,

Haedo³

et al. 2011

Endocrine-Related Cancer

View full text Add to dashboard Cite

The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1a (HIF-1a). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of tumour neovascularisation. In this study, the expression and role of RSUME in pituitary tumours was studied. We found that RSUME mRNA was up-regulated in pituitary adenomas and significantly correlated with HIF-1a mRNA levels. Hypoxia (1% O 2 ) or treatment with hypoxia-mimicking CoCl 2 enhanced RSUME and HIF-1a expression, induced translocation of HIF-1a to the nuclei and stimulated VEGF-A production both in pituitary tumour cell lines and primary human pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl 2 -induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1a synthesis. Thus, RSUME plays an important role in initiating pituitary tumour neovascularisation through regulating HIF-1a levels and subsequent VEGF-A production and may therefore be critically involved in pituitary adenoma progression.

show abstract