In vitro throughput screening of anticancer drugs using patient-derived cell lines cultured on vascularized three-dimensional stromal tissues.

Autor: Takahashi Y; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan; Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan., Morimura R; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan; Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan., Tsukamoto K; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan., Gomi S; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan., Yamada A; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan; Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan., Mizukami M; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan., Naito Y; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan; Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan., Irie S; Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan., Nagayama S; Department of Colorectal Surgery, Gastroenterological Cancer Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; Department of Surgery, Uji Tokushukai Medical Center, Kyoto 611-0041, Japan., Shinozaki E; Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan., Yamaguchi K; Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan., Fujita N; Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan., Kitano S; Business Development Division, Technical Research Institute, TOPPAN Holdings Inc., Saitama 345-8508, Japan; Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan. Electronic address: shiro.kitano@toppan.co.jp., Katayama R; Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. Electronic address: ryohei.katayama@jfcr.or.jp., Matsusaki M; Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan; Department of Applied Chemistry Graduate School of Engineering Osaka University, Osaka 565-0871, Japan. Electronic address: m-matsusaki@chem.eng.osaka-u.ac.jp.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Jul 15; Vol. 183, pp. 111-129. Date of Electronic Publication: 2024 May 25.
DOI: 10.1016/j.actbio.2024.05.037
Abstrakt: The development of high-throughput anticancer drug screening methods using patient-derived cancer cell (PDC) lines that maintain their original characteristics in an in vitro three-dimensional (3D) culture system poses a significant challenge to achieving personalized cancer medicine. Because stromal tissue plays a critical role in the composition and maintenance of the cancer microenvironment, in vitro 3D-culture using reconstructed stromal tissues has attracted considerable attention. Here, a simple and unique in vitro 3D-culture method using heparin and collagen together with fibroblasts and endothelial cells to fabricate vascularized 3D-stromal tissues for in vitro culture of PDCs is reported. Whereas co-treatment with bevacizumab, a monoclonal antibody against vascular endothelial growth factor, and 5-fluorouracil significantly reduced the survival rate of 3D-cultured PDCs to 30%, separate addition of each drug did not induce comparable strong cytotoxicity, suggesting the possibility of evaluating the combined effect of anticancer drugs and angiogenesis inhibitors. Surprisingly, drug evaluation using eight PDC lines with the 3D-culture method resulted in a drug efficacy concordance rate of 75% with clinical outcomes. The model is expected to be applicable to in vitro throughput drug screening for the development of personalized cancer medicine. STATEMENT OF SIGNIFICANCE: To replicate the cancer microenvironment, we constructed a cancer-stromal tissue model in which cancer cells are placed above and inside stromal tissue with vascular network structures derived from vascular endothelial cells in fibroblast tissue using CAViTs method. Using this method, we were able to reproduce the invasion and metastasis processes of cancer cells observed in vivo. Using patient-derived cancer cells, we assessed the possibility of evaluating the combined effect with an angiogenesis inhibitor. Further, primary cancer cells also grew on the stromal tissues with the normal medium. These data suggest that the model may be useful for new in vitro drug screening and personalized cancer medicine.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michiya Matsusaki, Ryohei Katayama and Eiji Shinozaki report that financial support was provided by TOPPAN Holdings Inc. Michiya Matsusaki, Ryohei Katayama, Shinji Irie, Satoshi Nagayama and TOPPAN Holdings Inc are inventors of several patents related to the CAViTs method. Yuki Takahashi, Rii Morimura, Kei Tsukamoto, Sayaka Gomi, Asuka Yamada, Miki Mizukami, Yasuyuki Naito and Shiro Kitano are employees of TOPPAN Holdings Inc.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: