Yusaku Hori1,2, Ken Ito2,3, Shusei Hamamichi2, Yoichi Ozawa1, Junji Matsui1, Izumi O Umeda2, Hirofumi Fujii4. 1. Biology Research, Oncology Tsukuba Research Department, Eisai Co., Ltd., Tsukuba, Japan. 2. Division of Functional Imaging, National Cancer Center, Kashiwa, Japan. 3. Halichondrin Research, Oncology Tsukuba Research Department, Eisai Co., Ltd., Tsukuba, Japan. 4. Division of Functional Imaging, National Cancer Center, Kashiwa, Japan hifujii@east.ncc.go.jp.
Abstract
BACKGROUND/AIM: Tumor angiogenesis induced by vascular endothelial growth factor (VEGF) and/or fibroblast growth factor (FGF) plays an important role in tumor growth, metastasis, and drug resistance. However, the characteristics of tumor vessels derived from these angiogenic factors have not been fully explored. MATERIALS AND METHODS: To functionally examine tumor vessels, we developed in vivo VEGF- and FGF-induced tumor blood vessel models. We performed immunohistochemistry and Hoechst perfusion assay to elucidate histopathological differences between the derived tumor vessels. To kinetically understand tumor perfusion, we employed radiolabeled PEGylated liposomes. RESULTS: While tumor vessel density was substantially increased by enhanced expression levels of VEGF and FGF, permeability of VEGF-driven tumor vessels was significantly higher than that of FGF-driven ones, the latter demonstrating an increased number of pericyte-covered vessels. Accordingly, we observed an increased tumor retention of the PEGylated liposomes in the VEGF-driven tumor. CONCLUSION: Our in vivo models of tumor vessel demonstrate the frequency of pericyte coverage and tumor perfusion levels as major functional differences between VEGF- and FGF-driven tumor vessels. Copyright
BACKGROUND/AIM: Tumor angiogenesis induced by vascular endothelial growth factor (VEGF) and/or fibroblast growth factor (FGF) plays an important role in tumor growth, metastasis, and drug resistance. However, the characteristics of tumor vessels derived from these angiogenic factors have not been fully explored. MATERIALS AND METHODS: To functionally examine tumor vessels, we developed in vivo VEGF- and FGF-induced tumor blood vessel models. We performed immunohistochemistry and Hoechst perfusion assay to elucidate histopathological differences between the derived tumor vessels. To kinetically understand tumor perfusion, we employed radiolabeled PEGylated liposomes. RESULTS: While tumor vessel density was substantially increased by enhanced expression levels of VEGF and FGF, permeability of VEGF-driven tumor vessels was significantly higher than that of FGF-driven ones, the latter demonstrating an increased number of pericyte-covered vessels. Accordingly, we observed an increased tumor retention of the PEGylated liposomes in the VEGF-driven tumor. CONCLUSION: Our in vivo models of tumor vessel demonstrate the frequency of pericyte coverage and tumor perfusion levels as major functional differences between VEGF- and FGF-driven tumor vessels. Copyright
Authors: Xiaoyan Xu; Jianjun Wang; Chen Yan; Yingli Men; Huang Jiang; Huijuan Fang; Xianwei Xu; Jinhua Yang Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2020-11-30
Authors: Christa A M van der Fels; Selma Palthe; Henk Buikema; Marius C van den Heuvel; Annemarie Leliveld; Igle Jan de Jong Journal: Diagnostics (Basel) Date: 2020-09-15