Using size-controlled multicellular spheroids of murine adenocarcinoma cells to efficiently establish pulmonary tumors in mice

作者：Nishikawa Tomoko; Tanaka Yutaro; Kusamori Kosuke; Mizuno Narumi; Mizukami Yuya; Ogino Yuka; Shimizu Kazunori; Konishi Satoshi; Takahashi Yuki; Takakura Yoshinobu; Nishikawa Makiya^*

来源：Biotechnology Journal, 2017, 12(8): 1600513.

DOI：10.1002/biot.201600513

• Cancer cell
• Cell adhesion molecule
• Multicellular spheroid
• Pulmonary tumors
• Tumor-bearing animal model

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 m through a micromolding technique, and obtained colon26 spheroids with average diameters of 169, 240, 272, and 341 m, respectively. Small and medium spheroids were subsequently used. mRNA levels of integrin 1, CD44, and fibronectin, molecules involved in cell adhesion, increased with increasing colon26 spheroid size. Approximately 1.5 x 10(4) 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.

• 出版日期2017-8