Background: Small cell carcinoma of the esophagus is rare and its prognosis is extremely poor. However, there is currently no in vitro model of this disease.
Methods: After obtaining written informed consent, we obtained a tumor from a 56-year-old female patient with esophageal small cell carcinoma in 2009 and transplanted it into a Severe Combined Immuno Deficiency (SCID) mouse. After successful transplantation, a tumor from the back of this mouse was minced with a sharp scissors without enzymes and was cultured in Ham F12/DMDM supplemented with 5% fetal bovine serum.
Results: Culture cells grew as adherent cells during the initial culture phase and gradually grew as floating aggregated cells. We carefully maintained these floating cells and transferred them without enzymes. These cells could passage to another flask with a split ratio of 1/10. We named these cells “TYUC-1”, and passaged them more than 85 times. The population doubling-time of TYUC-1 was approximately 30 hours. The G-band karyotype confirmed that these cells had a human origin. These cells could be transplanted to SCID mice with the same histological features of primary esophageal small cell carcinoma, and were shown to express TrkA, NGF, NSE, FGFRL1, p53, CD56, ALDH1A1, and CD44, but not CD133. A cDNA array also revealed that 9 genes were overexpressed while the expression of 33 genes was significantly lower than that in 28 esophageal squamous cell carcinoma (ESCC) cell lines. Whole exome sequencing revealed that TYUC-1 had TP53, PIK3CA, KMT2D, CACNA1H, NCOR1 and HRAS mutations. Furthermore, TYUC-1 had mutations in 128 genes, whereas 28 ESCC cell lines had no mutations in these genes.
Conclusions: We newly established TYUC-1 cells that exhibited neuroendocrine characteristics and expressed several stem cell-related molecules. These cells may be useful for understanding the characteristics of esophageal small cell carcinoma.
Citation Format: Yutaka Shimada, Tomoyuki Okumura, Yoshinori Takei, Kazuaki Watanabe, Akira Hirasawa, Arito Yamane, Masahiko Nishiyama, Takuya Nagata, Kazuhiro Tsukada, Kazuharu Shimizu. Establishment of an esophageal small cell carcinoma cell line (TYUC-1). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5126. doi:10.1158/1538-7445.AM2015-5126