TY - JOUR
T1 - Vascularized cancer on a chip
T2 - The effect of perfusion on growth and drug delivery of tumor spheroid
AU - Nashimoto, Yuji
AU - Okada, Ryu
AU - Hanada, Sanshiro
AU - Arima, Yuichiro
AU - Nishiyama, Koichi
AU - Miura, Takashi
AU - Yokokawa, Ryuji
N1 - Funding Information:
This work was supported by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST, Grant Number JPMJCR14W4 ); Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 25600060 , 16K16386 ); Mizuho Foundation for the Promotion of Sciences; Research Grant from the Nakatomi Foundation; and Japan Agency for Medical Research and Development (AMED). The authors acknowledge the Center for Anatomical, Pathological and Forensic Medical Researches, Kyoto University Graduate School of Medicine, for preparing the microscope slides. We appreciate Prof. Shuichi Takayama and Prof. Gary Lucker for the donation of MDA-MB-231. Microfabrication was supported by Kyoto University Nano Technology Hub. The authors thank A. Kawasaki and M. Moriwake for their assistance in fabricating the microfluidic devices and in capturing the images of the histological and immunohistochemical sections. We would like to thank Editage ( www.editage.com ) for English language editing. Appendix A
Funding Information:
This work was supported by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST, Grant Number JPMJCR14W4); Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 25600060, 16K16386); Mizuho Foundation for the Promotion of Sciences; Research Grant from the Nakatomi Foundation; and Japan Agency for Medical Research and Development (AMED). The authors acknowledge the Center for Anatomical, Pathological and Forensic Medical Researches, Kyoto University Graduate School of Medicine, for preparing the microscope slides. We appreciate Prof. Shuichi Takayama and Prof. Gary Lucker for the donation of MDA-MB-231. Microfabrication was supported by Kyoto University Nano Technology Hub. The authors thank A. Kawasaki and M. Moriwake for their assistance in fabricating the microfluidic devices and in capturing the images of the histological and immunohistochemical sections. We would like to thank Editage (www.editage.com) for English language editing.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2020/1
Y1 - 2020/1
N2 - Tumor vasculature creates a hostile tumor microenvironment (TME) in vivo and nourishes cancers, resulting in cancer progression and drug resistance. To mimic the biochemical and biomechanical environments of tumors in vitro, several models integrated with a vascular network have been reported. However, the tumor responses to biochemical and biomechanical stimuli were evaluated under static conditions and failed to incorporate the effects of blood flow to tumors. In this study, we present a tumor-on-a-chip platform that enables the evaluation of tumor activities with intraluminal flow in an engineered tumor vascular network. The fibroblasts in the tumor spheroid induced angiogenic sprouts, which constructed a perfusable vascular network in a tumor spheroid. The perfusability of the engineered vascular network was preserved during the culture. Moreover, perfusion for over 24 h significantly increased the proliferation activities of tumor cells and decreased cell death in the spheroid. Drug administration under perfusion condition did not show the dose-dependent effects of anticancer drugs on tumor activities in contrast to the results under static conditions. Our results demonstrate the importance of flow in a vascular network for the evaluation of tumor activities in a drug screening platform.
AB - Tumor vasculature creates a hostile tumor microenvironment (TME) in vivo and nourishes cancers, resulting in cancer progression and drug resistance. To mimic the biochemical and biomechanical environments of tumors in vitro, several models integrated with a vascular network have been reported. However, the tumor responses to biochemical and biomechanical stimuli were evaluated under static conditions and failed to incorporate the effects of blood flow to tumors. In this study, we present a tumor-on-a-chip platform that enables the evaluation of tumor activities with intraluminal flow in an engineered tumor vascular network. The fibroblasts in the tumor spheroid induced angiogenic sprouts, which constructed a perfusable vascular network in a tumor spheroid. The perfusability of the engineered vascular network was preserved during the culture. Moreover, perfusion for over 24 h significantly increased the proliferation activities of tumor cells and decreased cell death in the spheroid. Drug administration under perfusion condition did not show the dose-dependent effects of anticancer drugs on tumor activities in contrast to the results under static conditions. Our results demonstrate the importance of flow in a vascular network for the evaluation of tumor activities in a drug screening platform.
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U2 - 10.1016/j.biomaterials.2019.119547
DO - 10.1016/j.biomaterials.2019.119547
M3 - Article
C2 - 31710953
AN - SCOPUS:85074672243
SN - 0142-9612
VL - 229
JO - Biomaterials
JF - Biomaterials
M1 - 119547
ER -
