Expression of receptor tyrosine kinases VEGFR‐1 (FLT‐1), VEGFR‐2 (KDR), EGFR‐1, PDGFRa and c‐Met in canine primary brain tumours

Abstract

Inhibition of tumour growth and angiogenesis by targeting key growth factor receptors is a promising therapeutic strategy for central nervous system tumours. Characterization of these growth factor receptors in canine primary brain tumours has not been done. Using quantitative real-time TaqMan polymerase chain reaction (PCR), we evaluated the expression of messenger RNA (mRNA) for five tyrosine kinase growth factor receptors (vascular endothelial growth factor receptor [VEGFR]-1, VEGFR-2, endothelial growth factor receptor [EGFR]-1, platelet-derived growth factor receptor a [PDGFRa], and c-Met) relative to normal cerebral cortex in 66 spontaneous canine primary brain tumours. Increased expression of VEGFR-1 and VEGFR-2 mRNA was greatest in grade IV astrocytomas (glioblastoma multiforme) and grade III (anaplastic) oligodendrogliomas. EGFR-1 mRNA expression was more consistently increased than the other receptors in all tumour types, while increased PDGFRa mRNA expression was mostly restricted to oligodendrogliomas. The similarities in increased expression of these tyrosine kinase growth factor receptors in these canine tumours, as compared to data from their human counterparts, suggest that common molecular mechanisms may be present.

Advances in Diagnostic and Treatment Modalities for Intracranial Tumors

“…Veterinary trials with toceranib and masitinib have shown benefit in several cancers but have not been reported for brain tumors. Documented overexpression of VEGF, VEGF receptors, and PDGFR alpha in some canine brain tumors108, 109, 110, 111, 112, 113, 114, 115, 116 may justify trials with these or similar small molecules in defined patients.…”

Canine Astrocytic Tumors

“…29,63,82 In contrast, in a population of 11 dogs with varying grades of astrocytoma, minimal increases in PDGFRa mRNA were detected in tumor tissue compared with controls. 16 Recently, overexpression of PDGFRa was demonstrated by tissue microarray immunophenotyping in 43% (3 of 7) of GBMs, 20% (1 of 5) of grade III canine astrocytomas, and 14% (1 of 7) of grade II canine astrocytomas. 26 In people with astrocytoma, the prognostic and predictive value of PDGFRa expression within tumor tissue is controversial and clouded by inconsistencies in patient populations, analytic methods, and study design.…”

“…27 Both VEGFR-1 and VEGFR-2 mRNA have also been identified in astrocytic tumors from dogs, although among 23 kinds of canine astrocytic neoplasia, expression levels did not significantly differ on the basis of tumor grade. 16 In people, astrocytic tumor VEGF expression has not been shown to be an independent prognostic biomarker associated with survival. 21,30,40,55 The value of VEGF and VEGFR as predictive or prognostic biomarkers in dogs with astrocytic neoplasia has not been examined.…”

“…40,59 As is the case in people, the concentration of intratumoral VEGF in dogs with astrocytic neoplasia increases with tumor grade. 16,65 Three canine VEGF mRNA isoforms (VEGF 120 , VEGF 164 , VEGF 188 ) are recognized in astrocytic tumors, with VEGF 164 having the highest relative expression. 16 The expression of VEGF mRNA is significantly greater in tumor tissue of dogs with GBM (grade IV) compared with dogs with grade II astrocytoma.…”

“…16,65 Three canine VEGF mRNA isoforms (VEGF 120 , VEGF 164 , VEGF 188 ) are recognized in astrocytic tumors, with VEGF 164 having the highest relative expression. 16 The expression of VEGF mRNA is significantly greater in tumor tissue of dogs with GBM (grade IV) compared with dogs with grade II astrocytoma. 17 High-grade human astrocytic tumors, especially GBM, have greater concentrations of VEGFR-1 and VEGFR-2 mRNA, compared with low-grade astrocytomas.…”