Cancer stem cells (CSCs) have been hypothesized to drive the growth, metastasis and chemoresistance capacity. Activation of sonic hedgehog (SHH) signaling has been implicated in progression of variety of tumors. In this study, we investigated potentiality that activation of the SHH pathway maintained the characteristics of gastric CSCs. First, we establish spheres culture system from 5 human gastric cancer cells and identified spheres from 3 gastric CSCs (MKN45, SNU638, SNU601). Compared with parent cells, spheres had more self-renewing capacity and multipotent capacity. Gastric cancer spheres shown that increased expression of stem cell markers (Oct4 and Nanog) and decreased epithelial maker (Cytokeratin 18). However, expressions of CSCs markers (CD44, CD24, CD54 and CD133) were not significantly. Spheres showed more CSCs characteristics, such as more colony formation and more resistance to conventional chemotherapeutic drugs (5-FU, cisplatin and paclitaxel) compared to parent cells. Next, western blot showed that the expression levels of SHH related pathway (Ptch, Smo and Gli1) were significantly higher in spheres than in parent cells. Further analysis, we found that SHH pathway blocked by cyclopamine enhanced the efficacy of chemotherapeutic drugs in spheres. In the further study, we will confirm SHH dependence and in vivo xenograft study. In conclusion, our data suggest that sonic hedgehog blockade could improve the antitumor efficacy of chemotherapy of human gastric cancer. [This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. A010250)]

Citation Format: Jae Sook Sung, Jong Won Lee, Ukhyun Jo, Yeul Hong Kim. Association with the sonic hedgehog pathway between gastric cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3746. doi:10.1158/1538-7445.AM2013-3746