Abstract 4865: The functional and clinicopathological analysis of hypoxia inducible factor-1α (HIF1-α) in head and neck squamous cell carcinoma

Abstract

Abstract Introduction: Tumor hypoxia is considered to be associated with progression in various cancers. Hypoxia inducible factor-1α (HIF-1α) is one of the molecules which play a key role in tumor hypoxia. High HIF-1α expression is reported to have an impact on poor prognosis and resistance to chemotherapy or radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the effect and mechanism of HIF-1α on tumor metastasis in HNSCC is still unclear. The aim of the present study was to investigate the molecular targets of HIF1-α relevant to metastasis, and to reveal the impact of HIF1-α on HNSCC metastasis by using clinicopathological assays. Methods: The cell proliferation rate with or without HIF-1 inhibitor (KC7F2) in HNSCC cell lines (FaDu, Detroit512) was evaluated by MTS assay. Gene expression levels related to epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) and HIF-1α in each HNSCC cell lines were measured by quantitative real-time PCR. Immunohistochemical expressions of HIF-1α and clinicopathological factors were analyzed using surgical specimens from 33 patients with hypopharyngeal carcinoma who had undergone trans-oral tumor resection without previous chemotherapy nor radiotherapy. Results: HIF-1 inhibitor suppressed the cell growth of HNSCC cell lines in a dose dependent manner. HIF-1 inhibitor downregulated the expression of HIF-1α, twist, Oct3/4 and Nanog. In immunohistochemical study, the HIF-1α expression was higher in cancer cells than in normal cells of the adjacent normal mucosa. Univariate analysis revealed that high expression of HIF-1α was significantly correlated with T-classification (P=0.012), lymph node metastasis (P=0.002) and lymphatic invasion (P=0.03). Conclusion: These results suggest that HIF-1α plays a key role in tumor progression of HNSCC through EMT and CSC properties. From the present study, HIF-1α inhibition may have the possibility to suppress tumor metastasis, making HIF-1α an attractive target for the treatment of HNSCC. Citation Format: Yuichi Ikari, Hiroyuki Ozawa, Yorihisa Imanishi, Toshiki Tomita, Mariko Sekimizu, Yoshihiro Watanabe, Fumihiro Ito, Shin Saito, Kaoru Ogawa. The functional and clinicopathological analysis of hypoxia inducible factor-1α (HIF1-α) in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4865. doi:10.1158/1538-7445.AM2017-4865