Abstract 4257: Establishment of cancer-tissue originated spheroids (CTOSs) and chemo-sensitivity test for endometrial cancer
Authors: Kimura Toshihiro , Yoshino Kiyoshi , Hiramatsu Kosuke , Kiyohara Yumiko , Morimoto Akiko , Yokoyama Takuhei , Kobayashi Eiji , Ueda Yutaka , Fujita Masami , Inoue Masahiro , Enomoto Takayuki , Kimura Tadashi 
Published: August 2012

[Background] Endometrial cancer is one of the most common malignancy of the female genital tract in Japan, and the frequency is increasing year by year. Surgical therapy is performed as initial treatment for most of the patients. Pathological staging according to the surgical findings and the pathological findings is the most important prognostic factors. Several trials of adjuvant radiation and/or chemotherapy have been conducted for high-risk patients, but so far no standard regimen is confirmed. In this study, we established a chemo-sensitivity test for endometrial cancer using cancer-tissue originated spheroids (CTOSs). This chemo-sensitivity test can find not only the best regimen for endometrial cancer but also personalized medicine in the future. [Materials and Methods] A new primary culture system has been reported in colon cancer. These cells are called CTOS (cancer-tissue originated spheroids), in which cell-cell contact of cancer cells is retained throughout the process. By the CTOS method, highly purified and viable primary colorectal cancer cells are effectively prepared and cultured in vitro. Fresh cancerous tissues were removed from a series of 10 patients with endometrial cancer. Surgical and pathological findings revealed that 6 cases were Stage I, 1 case was Stage II, 3 cases were Stage III, 0 case was Stage IV. For histological classification, all of them were endometrioid adenocarcinoma (G1; 4 cases, G2; 4 cases, G3; 2 cases). Cancer tissues were removed and prepared as previously described by Kondo et al (PNAS, 2011). Briefly, primary culture cells are purified from the surgical specimen by mechanical and chemical treatment steps. These cells formed spheroids within 24 hours and can be cultured and expanded in stem cell culture medium. [Results] In our study, by day 14 spheroid formation was observed in 6 out of 10 cases (60%). Some of these spheroids were transplanted to subcutaneous of immune-deficient mice and formed tumors. These xenograft tumors showed quite similar appearance for their histopathology in comparison with their original tumor. For chemo-sensitivity test, spheroids were cultured in the medium with cisplatin at the day 7. The medium was changed at the day 8 exposing CTOSs to cisplatin for 1 day. The spheroids growth was inhibited in a dose-dependent manner. [Conclusion] For endometrial cancer, establishment of CTOSs allow us to analyze chemo-sensitivity as primary culture in high success rate. This approach gives a prediction of the efficacy of anti-cancer agents for personalized medicine.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4257. doi:1538-7445.AM2012-4257