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

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 VEGF(165). The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF(165) 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.

Figure 1

(A) Semaphorin, NRP and VEGF expressions in gliomas measured by quantitative real-time RT–PCR; (B) SEMA3C and SEMA3F expressions in men and women; (C) SEMA3D and VEGF expressions in low- and high-grade gliomas. Results are expressed by [2^−ΔC_t × 1000], where ΔC_t = C_ttarget − C_tGAPDH.

Figure 2

Kaplan–Meier survival curves for 38 patients with glial tumours, for SEMA3B (A), SEMA3G (B), VEGF (C) and NRP2 (D) expressions. Three groups of patients were defined as follows: group 1 included patients whose expression for the tested transcript was below the 25th quartile, group 2 for expression included between the 25th and 75th percentile values and group 3 for expression above the 75th quartile.