Abstract 179: Presence of primary cilia in cancer cells correlates with prognosis of pancreatic ductal adenocarcinoma

Abstract

Abstract Primary cilia are microtubule-based organelles that protrude from basal bodies and are involved in cell differentiation, sensory functions, and planar cell polarity. Especially, primary cilia have become popular as the place for signal transduction pathways including sonic hedgehog, Wnt, and platelet-derived growth factor pathways. Although there are many studies examining the roles of primary cilia in the fields of embryology and physiology, few such studies have been carried out in the field of oncology, and the role of primary cilia in cancer cells is poorly understood especially in human samples. In this study, we identified primary cilia by immunofluorescence analysis in which primary cilia were visualized as green rods labeled with anti-acetylated α-tubulin adjacent to basal bodies detected as red dots labeled with anti-γ-tubulin. Primary cilia were found in human pancreatic cancer cell lines (PANC-1 and CFPAC-1) and the number of them increased in the condition of serum starvation. As for clinical samples, primary cilia were found in cancer cells in 25 of 100 pancreatic ductal carcinoma patients [1-109 (median 8) primary cilia / 3 field pictures]. Most primary cilia in cancer tissue were observed in areas showing well differentiated glandular structures in clinical samples. Patients whose cancers were primary cilia positive had a higher frequency of lymph node metastasis than those whose cancers were primary cilia negative (p = 0.016). Univariate analysis demonstrated that tumor size (p = 0.009), tumor grade (p = 0.001), lymph node metastasis (p = 0.008), and the presence of primary cilia (p = 0.002) correlated with overall survival. Multivariate analysis found that tumor grade (p < 0.001) and the presence of primary cilia (p = 0.001) were independent prognostic indicators. In summary, we showed that pancreatic cancer cells can form primary cilia and that the presence of primary cilia is significantly associated with the prognosis of pancreatic ductal adenocarcinoma. The presence of primary cilia has the potential to become a new diagnostic tool and therapeutic target. Citation Format: Katsura Emoto, Yohei Masugi, Ken Yamazaki, Kathryn Effendi, Hanako Tsujikawa, Minoru Kitago, Osamu Itano, Yuko Kitagawa, Michiie Sakamoto. Presence of primary cilia in cancer cells correlates with prognosis of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 179. doi:10.1158/1538-7445.AM2014-179