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Using size‐controlled multicellular spheroids of murine adenocarcinoma cells to efficiently establish pulmonary tumors in mice
Authors:Tomoko Nishikawa  Yutaro Tanaka  Kosuke Kusamori  Narumi Mizuno  Yuya Mizukami  Yuka Ogino  Kazunori Shimizu  Satoshi Konishi  Yuki Takahashi  Yoshinobu Takakura  Makiya Nishikawa
Institution:1. Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan;2. Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan;3. Institute for Innovative NanoBio Drug Discovery and Development, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan;4. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Furo‐cho, Chikusa‐ku, Japan;5. Department of Mechanical Engineering, Ritsumeikan University, Kusatsu, Japan;6. Ritsumeikan‐Global Innovation Research Organization, Ritsumeikan University, Kusatsu, Japan
Abstract:Previous studies demonstrated that multicellular spheroids developed using polydimethylsiloxane‐based microwells exhibited superior functions, such as insulin secretion from pancreatic cells, over suspended cells. To successfully apply these spheroids, the effect of spheroid size on cellular functions must be determined. In this study, using murine adenocarcinoma colon26 cells, the authors examined whether such spheroids were useful for developing tumor‐bearing animal models, which requires the efficient and stable engraftment of cancer cells at implanted sites and/or metastatic sites. The authors prepared microwells with widths of 360, 450, 560, and 770 μm through a micromolding technique, and obtained colon26 spheroids with average diameters of 169, 240, 272, and 341 μm, respectively. Small and medium spheroids were subsequently used. mRNA levels of integrin β1, CD44, and fibronectin, molecules involved in cell adhesion, increased with increasing colon26 spheroid size. Approximately 1.5 × 104 colon26 cells in suspension or in spheroids were intravenously inoculated into BALB/c mice. At 21 days after inoculation, the lung weight of both colon26 spheroid groups, especially the group injected with small spheroids, was significantly higher than that of mice in the suspended colon26 cell group. These results indicate that controlling cancer cell spheroid size is crucial for tumor development in tumor‐bearing mouse models.
Keywords:Cancer cell  Cell adhesion molecule  Multicellular spheroid  Pulmonary tumors  Tumor‐bearing animal model
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