gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Article

Send article

Immunomodulation of basal and hypoxia-induced angiogenic factor production in pituitary tumor cells

Meeting Abstract

Search Medline for

  • Kristin Lucia - Max-Planck-Institut für Psychiatrie, Klinische Neuroendokrinologie, München
  • Yonghe Wu - Max-Planck-Institut für Psychiatrie, Klinische Neuroendokrinologie, München
  • Michael Buchfelder - Neurochirurgische Klinik, Universitätsklinikum Erlangen
  • Dominique Kuhlen - Neurochirurgische Klinik der Technischen Universität München
  • Günter K. Stalla - Max-Planck-Institut für Psychiatrie, Klinische Neuroendokrinologie, München
  • Ulrich Renner - Max-Planck-Institut für Psychiatrie, Klinische Neuroendokrinologie, München

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMO.06.04

doi: 10.3205/13dgnc049, urn:nbn:de:0183-13dgnc0494

Published: May 21, 2013

© 2013 Lucia et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective: In pituitary adenomas the exact role of angiogenesis in tumor development remains unclear. Pituitary tumor cells express components of the innate immune system such as the Toll-like receptor 4 (TLR-4), through which bacterial lipopolysaccharide (LPS) have been shown to enhance the intratumoral IL-6 production in pituitary adenomas. Here we have studied whether LPS is also able to influence the production of angiogenic factors (VEGF-A, IL-8) by pituitary tumor cells.

Method: Murine folliculo-stellate-like TtT/GF pituitary cells and primary cell cultures of more than 20 human pituitary adenomas (somatotroph and endocrine-inactive tumors) were treated with LPS under basal and hypoxia-mimicking conditions (cobalt chloride treatment). HIF-1alpha and NF-kappaB expression was then studied by Western Immunoblotting. VEGF-A and IL-8 were measured by ELISA. RT-PCR was conducted to verify the presence of TLR-4 and IL-8 receptors in human tumors.

Results: We observed that both LPS and cobalt chloride treatment strongly induced HIF-1alpha and NF-kappaB protein expression as well as VEGF-A and IL-8 secretion in all cell populations studied. This suggests that crosstalk mechanisms between hypoxic and inflammatory processes may exist in pituitary tumor cells, which explain the observed additive effects of hypoxia and LPS stimulation on angiogenic factor production in some adenoma cell cultures. An interesting dichotomy of the angiogenic response (VEGF-A and IL-8 production) between somatotroph and endocrine-inactive tumor subtypes following LPS stimulation was observed, suggesting possible tumor-specific mechanisms of inflammatory responses.

Conclusions: We speculate that bacterial inflammation/infection may play a role in angiogenesis in pituitary tumors. This not only provides the basis for further investigation of inflammation-induced angiogenesis, but also provides insight into the mechanisms of angiogenesis in pituitary adenomas in general, which when further understood may provide improved options for treatment and prevention.