Abstract 2847: Tenascin C expression in neural microenvironment enhances perineural invasion and is associated with locoregional recurrence-related poor prognosis in pancreatic ductal adenocarcinoma

Abstract

Abstract Background: Perineural invasion (PNI) is commonly seen in pancreatic ductal adenocarcinoma (PDAC) and worsens the postoperative prognosis. However, the associated mechanisms in cancer progression remain unclear. Tenascin C (TNC), an extracellular matrix glycoprotein, is abundant in cancer stroma and modulates tumor progression. The aim of this study was to evaluate the functional roles of TNC in the neural microenvironment of PDAC. Methods: We immunohistochemically examined TNC expression in 78 resected PDAC specimens. TNC staining in perineural sites at the invasive front was classified as low or high intensity, by comparison with adjacent non-cancerous tissues in the same section. The relationships between TNC expression and clinicopathological features were retrospectively analyzed. Furthermore, interactions between cancer cells and nerves after supplementation with TNC were investigated when co-culturing a PDAC cell line with a mouse dorsal root ganglion (DRG) in vitro. Results: High perineural TNC expression at the invasive front, seen in 30 (38%) patients, was associated with PNI (p = 0.006), pathological T stage ≥ 3 (p = 0.01), and postoperative locoregional recurrence (p = 0.002). It was independently associated with postoperative, poor recurrence-free survival in multivariate analysis (p = 0.045). In the in vitro co-culture model, supplementation with TNC significantly enhanced both neurotropism of PDAC cells and tumor tropism of a DRG. On the other hand, when PDAC cells and a DRG were cultured separately, TNC did not affect cancer cell proliferation or neural outgrowth. Conclusions: Strong perineural TNC expression was a prognostic indicator of locoregional recurrence-related poor prognosis. The neurotropism of PDAC induced by TNC suggests that TNC could serve as a therapeutic target for PDAC. Citation Format: Satoru Furuhashi, Takanori Sakaguchi, Tomohiro Murakami, Mayu Fukushima, Yoshifumi Morita, Koji Ikegami, Hirotoshi Kikuchi, Megumi Baba, Mitsutoshi Setou, Hiyoya Takeuchi. Tenascin C expression in neural microenvironment enhances perineural invasion and is associated with locoregional recurrence-related poor prognosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2847.