Abstract
Abstract Patients with advanced head and neck squamous cell carcinoma (HNSCC) show poor prognosis to current therapy and tumor recurrence and metastasis are frequently observed. The discovery of cancer stem cell (CSC) markers is crucial for developing novel therapeutic strategies by targeting these CSCs. To address this issue, we used sphere culture method to enrich CSCs from their isogeneic adherent cultured HNSCC cells. Compared with adherent cultured HNSCC cells, the microspheres of HNSCC cells were more clonogenic in nude mice, and expressed higher levels of shh and Gli-2, and Gli-2 translocated into the nuclear of the spheres, which showed that hedgehog signal pathway was activated in the cancer stem cells like subpopulations of HNSCC. Further study found that Gli-2, one of the main transcriptional activators of HH/GLI signal, was expressed in 60 (44%) of the 136 HNSCC samples and the expression was significantly associated with poor clinical outcomes. Only 44% of the patients whose tumors expressed Gli-2 survived at 5 years after surgery compared to 77% of those whose tumors lacked the Gli-2 expression (P < 0.0001). Both cyclopamine and GANT61 effectively inhibited Gli expression, slowed cell growth, promoted G1 arrest, increased apoptosis and inhibited migration of HNSCC cells. Together with the findings, we conclude that activation of HH/GLI pathway plays an important role in maintaining the stemness of HNSCC, and strongly associates with HNSCC progression, suggesting that a subset of OSCC patients may benefit from anti-HH/GLI therapies. Citation Format: Ming Yan. HH/GLI signaling as a new therapeutic target governs the stemness of head and neck 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 3722. doi:10.1158/1538-7445.AM2013-3722
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