Expression of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Their Receptors (Flt-1, Flk-1, and Flg-1) in Canine Vascular Tumors

Abstract

Abstract. Expression of vascular endothelial growth factor (VEGF), its receptors (flt-1 and flk-1), and basic fibroblast growth factor (bFGF) in canine hemangiosarcoma (HSA) and hemangiomas was investigated by immunohistochemical analysis. In addition, expression of the mRNAs of VEGF, flt-1, flk-1, and flg-1 (a receptor for bFGF), was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) with cRNA probes. VEGF, bFGF, flt-1, and flk-1 were immunohistochemically detected in the neoplastic cells in HSAs; the staining intensity was stronger in HSAs than in hemangiomas. On the other hand, the neoplastic cells in hemangiomas exhibited very weak or no expression of VEGF, although they showed moderate expression of flt-1 and flk-1. The mRNAs of VEGF, flt-1, flk-1, and flg-1 were detected in the neoplastic cells in HSAs by ISH and RT-PCR. However, VEGF mRNA was not detectable in the neoplastic cells in hemangiomas by ISH, although it was detected in the inflammatory cells in the tumors by RT-PCR. Moreover, the HSAs that showed intense staining for flk-1 had a high proliferative activity, which was reflected as a high Ki-67 positive index. These results suggest that the expression of the growth factors and their receptors, especially flk-1, might be associated with the malignant proliferation of HSAs.

Vascular endothelial growth factor in prognosis of splenic malignant tumours in dogs

“…However, all haemangioma and haemangiosarcoma (HSA) endothelial cells showed cytoplasmic reactivity to VEGF, as indicated by the large number of positively stained cells. Similar results were obtained by Yonemaru et al (21). They demonstrated that the percentage of cells showing VEGF expression was significantly higher in haemangisarcomas than in haemangiomas (P < 0.05), and the expression of VEGF and Flk-1 receptor may be related to the proliferation of haemangiosarcoma cells.…”

Vascular-targeted agents for the treatment of angiosarcoma

“…Similar to the immunohistochemistry results presented here, other studies have shown that canine angiosarcomas express increased VEGF and VEGFR2 compared to haemangiomas, and also express increased VEGFR1 and bFGF [229]. These findings contrast with those from the immunohistochemistry analysis of the human vascular tumours.…”

Distribution of VEGF and flt-1 in the Normal Dog Tissues

“…Although flt-1 has less tyrosine kinase activity than flk-1, some reports have demonstrated that increased flt-1 correlates with that of VEGF and tumor grade [10]. Yonemaru et al [12] recently reported that VEGF and its receptors might be associated with the malignant proliferation of canine hemangiosarcoma. In addition, flt-1 plays an important role in the pulmonary metastasis of tumors [3].…”