Annual Report 2017
Department of Innovative Seeds Evaluation
Tadashi Kondo, Tsutomu Ohta, Rieko Oyama, Fusako Kito, Yoko Takai, Marimu Sakumoto, Naoya Hirai
Introduction
The Department of Innovative Seeds Evaluation focuses on two projects; the establishment of a patient-derived cancer model of rare cancers, and the characterization of developed cancer models for the preclinical study. The patient-
derived cancer model is an essentially important
tool to evaluate the novel innovative seeds, and many anti-cancer drugs and biomarkers have been developed using patient-derived cancer models. However, patient-derived cancer models are available only in a limited portion of cancers. With this notion, we launched the project to establish and characterize patient-derived cancer models. One of the most important applications of patient-derived cancer models is the examination of the efficacy of anti-cancer drugs as a pre-clinical study. With rare cancers, the pre-
clinical study has been hampered because of the lack of patient-derived cancer models. Thus, we created the evaluation system for the efficacy of anti-cancer drugs using our original patient-
derived cancer models.
Research activities
The surgically dissected tumor tissues obtained in the National Cancer Center Hospital (NCCH) were used to develop patient-derived cancer models. Tumor tissues are quite diverse in terms of substances in the tissues and heterogeneity of cell populations depending on the original tissue samples, and methods for individual histology are required to establish cancer models. The molecular characterization is also important to use cancer models in the research. Because the molecular backgrounds are altered during the process of cancer model establishment, it is quite important to know how the developed cancer models retain the original molecular backgrounds. For this sake, we employ the multi-
omics approach. The DNA, RNA, and proteins are comprehensively and intensively examined, comparing the original tissue samples and the
established models. Our cancer models are included in the collaborative study with pharmaceutical companies. The research activity of our department is linked to that of the Division of Rare Cancer Research. The ideas and the fundamental research tools are shared between two laboratories for the development of novel innovative seeds.
Future prospects
Our research activities will benefit patients with rare cancers by contributing to the development of novel cancer drugs. We will establish more collaborative studies with companies as well as academic research groups.
List of papers published in January 2017 - March 2018
Journal
1. Shimada Y, Kohno T, Ueno H, Ino Y, Hayashi H, Nakaoku T, Sakamoto Y, Kondo S, Morizane C, Shimada K, Okusaka T, Hiraoka N. An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma. Oncologist, 22:158-164, 2017
2. Qiao Z, Shiozawa K, Kondo T. Proteomic approach toward determining the molecular background of pazopanib resistance in synovial sarcoma. Oncotarget, 8:109587-109595, 2017
3. Qiao Z, Kito F, Kondo T. Meta-analysis identifies endothelin-3 as a prognostic biomarker in gastrointestinal stromal tumors. J Sarcoma Res, 1:1001, 2017
4. Qiao Z, Tajima T, Kito F, Arai Y, Kawai A, Kondo T. Metastasis-associated gene signature in primary myxoid liposarcoma identified through a gene expression study. J Electrophoresis, 61:9-15, 2017
5. Qiao Z, Kito F, Takai Y, Oyama R, Kondo T. Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma. J Electrophoresis, 61:1-7, 2017
6. Sakumoto M, Takahashi M, Oyama R, Takai Y, Kito F, Shiozawa K, Qiao Z, Yoshida A, Endo M, Kawai A, Kondo T. Establishment and proteomic characterization of NCC-LMS1-C1, a novel cell line of primary leiomyosarcoma of the bone. Jpn J Clin Oncol, 47:954-961, 2017
7. Kikuta K, Kubota D, Yoshida A, Qiao Z, Morioka H, Nakamura M, Matsumoto M, Chuman H, Kawai A, Kondo T. Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling. Biochim Biophys Acta, 1865:1160-1166, 2017
8. Oyama R, Takahashi M, Yoshida A, Sakumoto M, Takai Y, Kito F, Shiozawa K, Qiao Z, Arai Y, Shibata T, Araki Y, Endo M, Kawai A, Kondo T. Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines. Sci Rep, 7:4712, 2017
9. Asano N, Yoshida A, Mitani S, Kobayashi E, Shiotani B, Komiyama M, Fujimoto H, Chuman H, Morioka H, Matsumoto M, Nakamura M, Kubo T, Kato M, Kohno T, Kawai A, Kondo T, Ichikawa H. Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Oncotarget, 8:12941-12952, 2017
10. Kondo T. Current status of proteomics of soft tissue sarcomas. Expert Rev Proteomics, 14:1131-1140, 2017
11. Takai Y, Oyama R, Kito F, Sakumoto M, Shiozawa K, Qiao Z, Nakajima K, Takahashi M, Yoshida A, Setsu N, Kobayashi E, Kawai A, Kondo T. Establishment and characterization of a patient-derived cancer model of undifferentiated pleomorphic sarcoma. Tiss Cult Res Commun, 36:41-48, 2017
12. Shiozawa K, Shuting J, Yoshioka Y, Ochiya T, Kondo T. Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma. Biochem Biophys Res Commun, 495:1322-1327, 2018
13. Sakumoto M, Oyama R, Takahashi M, Takai Y, Kito F, Shiozawa K, Qiao Z, Endo M, Yoshida A, Kawai A, Kondo T. Establishment and proteomic characterization of patient-derived clear cell sarcoma xenografts and cell lines. In Vitro Cell Dev Biol Anim, 54:163-176, 2018