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Fan B.-L.,Xinxiang Medical University | Wu X.-S.,Xinxiang 371 Central Hospital | Mu L.-M.,Xinxiang Medical University | Zhu W.-L.,Xinxiang Medical University
Molecular Medicine Reports | Year: 2015

A chimeric plasminresistant vascular endothelial growth factor (VEGF)165/VEGF192 (132-158) protein, named as VEGF192 (according to the nomenclature of VEGF), designed by a previous study, was demonstrated to have an enhanced affinity for the extracellular matrix (ECM) amongst other bioactivities. However, it is now accepted that mutant VEGFs frequently demonstrate different angiogenic activities and produce different vascular patterning from the parental molecule. The present study hypothesized that VEGF192, due to its enhanced binding affinity to the ECM, would exhibit a different angiogenic activity and produce a different vascular patterning compared to those of VEGF165. Murine breast cancer EMT6 cells were manipulated to stably overexpress VEGF165 or VEGF192. These cells were then inoculated intradermally into BALB/c mice in order to monitor the formation of vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments revealed that overexpression of VEGF192 in murine breast cancer cells resulted in irregular, disorganized and dense vascular patterning as well as induced a significant inhibition of tumor growth compared with that of VEGF165. In addition, allograft tumor immunochemical assays of VEGF192overexpressing tumors demonstrated significantly lower vascular densities than those of VEGF165overexpressing tumors; however, VEGF192 tumors had a significantly enlarged vascular caliber. Conversely, cell wound healing experiments revealed that VEGF192overexpressing EMT6 cells had significantly decreased migration rates compared with those of VEGF165overexpressing EMT6 cells. In conclusion, the results of the present study supported the hypothesis that the altered ECM affinity of VEGF induced structural alterations to vasculature. In addition, these results provided a novel insight into VEGF design and indirect evidence for the function of exon 8 in VEGF.


PubMed | Xinxiang 371 Central Hospital and Xinxiang Medical University
Type: Journal Article | Journal: Molecular medicine reports | Year: 2014

A chimeric plasminresistant vascular endothelial growth factor (VEGF)165/VEGF183 (132-158) protein, named as VEGF183 (according to the nomenclature of VEGF), designed by a previous study, was demonstrated to have an enhanced affinity for the extracellular matrix (ECM) amongst other bioactivities. However, it is now accepted that mutant VEGFs frequently demonstrate different angiogenic activities and produce different vascular patterning from the parental molecule. The present study hypothesized that VEGF183, due to its enhanced binding affinity to the ECM, would exhibit a different angiogenic activity and produce a different vascular patterning compared to those of VEGF165. Murine breast cancer EMT6 cells were manipulated to stably overexpress VEGF165 or VEGF183. These cells were then inoculated intradermally into BALB/c mice in order to monitor the formation of vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments revealed that overexpression of VEGF183 in murine breast cancer cells resulted in irregular, disorganized and dense vascular patterning as well as induced a significant inhibition of tumor growth compared with that of VEGF165. In addition, allograft tumor immunochemical assays of VEGF183overexpressing tumors demonstrated significantly lower vascular densities than those of VEGF165overexpressing tumors; however, VEGF183 tumors had a significantly enlarged vascular caliber. Conversely, cell wound healing experiments revealed that VEGF183overexpressing EMT6 cells had significantly decreased migration rates compared with those of VEGF165overexpressing EMT6 cells. In conclusion, the results of the present study supported the hypothesis that the altered ECM affinity of VEGF induced structural alterations to vasculature. In addition, these results provided a novel insight into VEGF design and indirect evidence for the function of exon 8 in VEGF. [Corrected]

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