PMID- 32132519
OWN - NLM
STAT- MEDLINE
DCOM- 20210225
LR  - 20210225
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 49
IP  - 3
DP  - 2020 Mar
TI  - Tenascin C in the Tumor-Nerve Microenvironment Enhances Perineural Invasion and 
      Correlates With Locoregional Recurrence in Pancreatic Ductal Adenocarcinoma.
PG  - 442-454
LID - 10.1097/MPA.0000000000001506 [doi]
AB  - 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.
FAU - Furuhashi, Satoru
AU  - Furuhashi S
FAU - Sakaguchi, Takanori
AU  - Sakaguchi T
AD  - From the Second Department of Surgery.
FAU - Murakami, Tomohiro
AU  - Murakami T
AD  - From the Second Department of Surgery.
FAU - Fukushima, Mayu
AU  - Fukushima M
AD  - Pathology.
FAU - Morita, Yoshifumi
AU  - Morita Y
AD  - From the Second Department of Surgery.
FAU - Ikegami, Koji
AU  - Ikegami K
FAU - Kikuchi, Hirotoshi
AU  - Kikuchi H
AD  - From the Second Department of Surgery.
FAU - Setou, Mitsutoshi
AU  - Setou M
FAU - Takeuchi, Hiroya
AU  - Takeuchi H
AD  - From the Second Department of Surgery.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (TNC protein, human)
RN  - 0 (Tenascin)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Biomarkers, Tumor/*metabolism
MH  - Carcinoma, Pancreatic Ductal/*metabolism/secondary/surgery
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Female
MH  - Ganglia, Spinal/metabolism/pathology
MH  - Humans
MH  - Male
MH  - Mice, Inbred ICR
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - *Neoplasm Recurrence, Local
MH  - Pancreatic Neoplasms/*metabolism/pathology/surgery
MH  - Peripheral Nerves/*metabolism/pathology
MH  - Retrospective Studies
MH  - Tenascin/*metabolism
MH  - Treatment Outcome
MH  - *Tumor Microenvironment
EDAT- 2020/03/07 06:00
MHDA- 2021/02/26 06:00
CRDT- 2020/03/06 06:00
PHST- 2020/03/07 06:00 [pubmed]
PHST- 2021/02/26 06:00 [medline]
PHST- 2020/03/06 06:00 [entrez]
AID - 00006676-202003000-00018 [pii]
AID - 10.1097/MPA.0000000000001506 [doi]
PST - ppublish
SO  - Pancreas. 2020 Mar;49(3):442-454. doi: 10.1097/MPA.0000000000001506.