Effects of expressions of VEGF, VEGF ⁃ C, VEGFR ⁃ 3 on interstitial angiogenesis and tumor cell proliferation in human gliomas

Abstract

Objective To explore the changes of vascular endothelial growth factor (VEGF), vascular endothelial growth factor⁃C (VEGF⁃C) and vascular endothelial growth factor receptor⁃3 (VEGFR⁃3) expression and their impacts on tumor cell proliferation and interstitial angiogenesis in gliomas. Methods The specimens of 20 cases of WHO grade Ⅰ -Ⅱ, 20 cases of grade Ⅲ and 20 cases of grade Ⅳ gliomas were collected from Department of Neurosurgery in Tianjin Medical University General Hospital during the period from 2000 to 2009. The expressions of VEGF, VEGF⁃C, VEGFR⁃3 and Ki⁃67 as well as the density of CD31 positive vessels were detected in 60 gliomas with different grades of malignancy by means of tissue microarray and immunohistochemistry. Results In the tumor cells and vascular endothelial cells of 60 patients with gliomas, the positive rate of VEGF, VEGF ⁃ C and VEGFR ⁃ 3 was 88.33% (53/60) and 100% (60/60), 100% (60/60) and 16.67% (10/60), and 100% (60/60) and 21.67% (13/60) of tumor cells, respectively. No significant differences were seen among groups in different grades (P > 0.05, for all). In grade Ⅰ-Ⅱ, gradeⅢ and gradeⅣ gliomas, the density of VEGF positive tumor cells was (17.65 ± 9.00), (37.30 ± 18.54) and (83.40 ± 22.98) positive cell number/0.05 mm2, the density of VEGF⁃C positive tumor cells was (38.00 ± 17.82), (79.30 ± 5.23) and (102.00 ± 13.07) positive cell number/0.05 mm2, the density of VEGFR⁃3 positive vessels was (3.65 ± 2.01), (10.50 ± 3.98) and (14.60 ± 7.29) positive vessel number/4 HF, the density of Ki⁃67 positive tumor cells was (9.30 ± 3.48), (31.15 ± 9.44) and (60.15 ± 13.60) positive cell number/0.05 mm2, and CD31 positive microvessels was (6.75 ± 2.24), (10.35 ± 2.98) and (14.30 ± 3.51) positive vessel number/4 HF, respectively. The differences of each parameter mentioned above were all significant among the groups in different grades (P < 0.05 or P < 0.01), and they were positively correlated with each other (r = 0.663-0.910, P < 0.01). Conclusion Over⁃expression of VEGF and VEGF⁃C was seen in glioma cells, and VEGFR⁃3 was also over⁃expressed in interstitial vascular endothelial cells. Their expression levels increased along with the grade of malignancy. The paracrine loops composed by them can induce interstitial angiogenesis and tumor cell proliferation, and thereby play a crucial role in the occurrence and progression of gliomas.

DOI：10.3969/j.issn.1672-6731.2010.04.017