Reference - Detail
| RRC ID | 81689 |
|---|---|
| Author | Furuhashi S, Sakaguchi T, Murakami T, Fukushima M, Morita Y, Ikegami K, Kikuchi H, Setou M, Takeuchi H. |
| Title | Tenascin C in the Tumor-Nerve Microenvironment Enhances Perineural Invasion and Correlates With Locoregional Recurrence in Pancreatic Ductal Adenocarcinoma. |
| Journal | Pancreas |
| Abstract |
OBJECTIVES:Perineural invasion is common in pancreatic ductal adenocarcinoma (PDAC) and worsens the postoperative prognosis. Tenascin C (TNC), an extracellular matrix glycoprotein, modulates tumor progression. We evaluated the functional roles of TNC, especially in perineural invasion of PDAC. METHODS:We examined immunohistochemical TNC expression in 78 resected PDAC specimens. The relationships between TNC expression and clinicopathological features were retrospectively analyzed. Interactions between cancer cells and nerves with TNC supplementation were investigated using an in vitro coculture model with PDAC cell line and mouse dorsal root ganglion (DRG). RESULTS:Tenascin C expression was predominant in perineural sites at the invasive tumor front. High perineural TNC expression in 30 patients (38%) was associated with perineural invasion, pathological T stage ≥3, and postoperative locoregional recurrence. High TNC expression was independently associated with postoperative, poor recurrence-free survival by multivariate analysis. In the in vitro coculture model, a TNC-rich matrix enhanced both PDAC cell colony extensions toward nerves and DRG axonal outgrowth toward cancer cell colonies, whereas TNC did not affect axonal outgrowth or cancer cell proliferation in separately cultured DRG and PDAC cells. CONCLUSIONS:Strong perineural TNC expression indicated poor prognosis with locoregional recurrence. The neurotropism of TNC-induced PDAC suggests that TNC is a potential PDAC therapeutic target. |
| Volume | 49(3) |
| Pages | 442-454 |
| Published | 2020-3-1 |
| DOI | 10.1097/MPA.0000000000001506 |
| PII | 00006676-202003000-00018 |
| PMID | 32132519 |
| MeSH | Aged Animals Biomarkers, Tumor / metabolism* Carcinoma, Pancreatic Ductal / metabolism* Carcinoma, Pancreatic Ductal / secondary Carcinoma, Pancreatic Ductal / surgery Cell Line, Tumor Coculture Techniques Female Ganglia, Spinal / metabolism Ganglia, Spinal / pathology Humans Male Mice, Inbred ICR Middle Aged Neoplasm Invasiveness Neoplasm Recurrence, Local* Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology Pancreatic Neoplasms / surgery Peripheral Nerves / metabolism* Peripheral Nerves / pathology Retrospective Studies Tenascin / metabolism* Treatment Outcome Tumor Microenvironment* |
| IF | 2.92 |
| Resource | |
| Human and Animal Cells | PANC-1(RCB2095) MIA Paca2(RCB2094) |