Molecular Diagnostics

British Journal of Cancer (2008) 99, 1153–1160. doi:10.1038/sj.bjc.6604641 www.bjcancer.com
Published online 9 September 2008

Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

L Karayan-Tapon1, M Wager2, J Guilhot3, P Levillain4, C Marquant1, J Clarhaut5, V Potiron5 and J Roche5

  1. 1Université de Poitiers, EA 3805, CHU de Poitiers, 2 rue de la Milétrie, BP 577, Poitiers F-86021, France
  2. 2Université de Poitiers, CHU de Poitiers, Service de Neurochirurgie, 2 rue de la Milétrie, BP 577, Poitiers F-86021, France
  3. 3Université de Poitiers, CHU de Poitiers, Clinical Investigation Center, CIC INSERM 802, 2 rue de la Milétrie, BP 577, Poitiers F-86021, France
  4. 4Université de Poitiers, CHU de Poitiers, Laboratoire d'Anatomo-Pathologie, 2 rue de la Milétrie, BP 577, Poitiers F-86021, France
  5. 5Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, 40 avenue du Recteur Pineau, Poitiers F-86022, France

Correspondence: Professor J Roche, Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Faculté des Sciences de Poitiers, 40 avenue du Recteur Pineau, Poitiers Cédex 86022, France. E-mail: joelle.roche@univ-poitiers.fr

Received 4 February 2008; Revised 27 May 2008; Accepted 4 August 2008; Published online 9 September 2008.

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Abstract

Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF165. The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF165 for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker.

Keywords:

adult gliomas, semaphorin, neuropilin, VEGF