Masahiro Inoue, M.D., Ph.D. Professor
Our research aims at understanding cancer biology and developing novel therapeutics and diagnostics against cancer. We have developed a novel culture system of cancer cells from patient tumors. We are currently focusing on various aspects of cancer, which are mostly lost in the cancer cell lines.
Research and EducationOur institute is one of the prominent cancer centers in Japan. We are able to investigate tumor samples with high quality medical records. We have developed a novel culture system of cancer cells from patient tumors, which is called CTOS (Cancer Tissue-Originated Spheroid). CTOS method enables us to study pure cancer cells in vitro, retaining original characters of patient cancer. We are currently focusing on 1) diversity of individual patient cancer (banking of CTOSs, and exploration of biomarkers base on the in vitro sensitivity assay), 2) differentiation (cell polarity, and plasticity between differentiation and stemness), 3) multicellular response (unit of response as a mass, not as a single cell), 4) metabolism (tumor dormancy in hypoxic and poor nutritional conditions). Major technical procedures are preparation, culture, preservation, and sensitivity assay of CTOS, image analysis, intracellular signaling, gene manipulation, and CTOS-derived xenografts. We accept graduate students from various universities.
Figure 1 Preparation of CTOSs
Tumor samples are mechanically and enzymatically digested and are filtered by a cell strainer. Tumor fragments upon the strainer are collected and cultured. The fragments forms sphere (CTOS) within a couple of hours.
Figure 2 CTOSs retain original characters of patient tumor
Most of the colorectal cancers are differentiated adenocarcinoma, which have gland-like structures. CTOSs retain the differentiation character in vitro, while conventional cancer cell lines generally lack the character. red：villin, green：E-cadherin, blue：DAPI
- Tashiro T, Okuyama H, Endo H, Kawada K, Ashida Y, Ohue M et al. In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer. PLoS One 2017; 12: e0174151.
- Endo H, Okami J, Okuyama H, Nishizawa Y, Imamura F, Inoue M. The induction of MIG6 under hypoxic conditions is critical for dormancy in primary cultured lung cancer cells with activating EGFR mutations. Oncogene 2016.
- Okuyama H, Kondo J, Sato Y, Endo H, Nakajima A, Piulats JM et al. Dynamic Change of Polarity in Primary Cultured Spheroids of Human Colorectal Adenocarcinoma and Its Role in Metastasis. Am J Pathol 2016; 186: 899-911.
- Kondo J, Endo H, Okuyama H, Ishikawa O, Iishi H, Tsujii M, Ohue M, Inoue M. Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc Natl Acad Sci USA, 2011; 108:6235-40
- Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15:220-31.
Department of Biochenmistry, Osaka International Cancer InstituteMasahiro Inoue
TEL 81-6-6945-1181, FAX 81-6-6945-1900