Fumio Nakamura    Department   School of Medicine, School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Low Incidence of High-Grade Pancreatic Intraepithelial Neoplasia Lesions in a Crmp4 Gene-Deficient Mouse Model of Pancreatic Cancer.
Journal	Formal name：Translational oncology Abbreviation：Transl Oncol ISSN code：19365233/19365233
Domestic / Foregin	Foregin
Volume, Issue, Page	13(3),pp.100746
Author and coauthor	Yazawa Keiichi, Daiki, Sato Sho, Hiroshima Yukihiko, Yabushita Yasuhiro, Mori Ryutaro, Matsuyama Ryusei, Kato Ikuma, Taniguchi Hideki, Goshima Yoshio, Endo Itaru
Authorship	2nd author
Publication date	2020/03
Summary	Pancreatic intraepithelial neoplasia (PanIN), the most common premalignant lesion of the pancreas, is a histologically well-defined precursor to invasive pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms underlying the progression of PanINs have not been fully elucidated. Previously, we demonstrated that the expression of collapsin response mediator protein 4 (CRMP4) in PDAC was associated with poor prognosis. The expression of CRMP4 was also augmented in a pancreatitis mouse model. However, the role of CRMP4 in the progression of PanIN lesions remains uncertain. In the present study, we examined the relationship between CRMP4 expression and progression of PanIN lesions using genetically engineered mouse models. PanIN lesions were induced by peritoneal injection of the cholecystokinin analog caerulein in LSL-KRASG12D; Pdx1-Cre (KC-Crmp4 wild-type, WT) mice and LSL-KRASG12D; Pdx1-Cre; Crmp4-/- (KC-Crmp4 knockout, KO) mice. We analyzed pancreatic tissue sections from these mice and evaluated PanIN grade by hematoxylin and eosin staining. CRMP4 expression was examined and the cellular components assessed by immunohistochemistry using antibodies against CRMP4, CD3, and α-smooth muscle actin (SMA). The incidence of high-grade PanIN in KC-Crmp4 WT mice was higher than that in KC-Crmp4 KO animals. CRMP4 was expressed not only in epithelial cells but also in αSMA-positive cells in stromal areas of PanIN lesions. The CRMP4 expression in stromal areas correlated with PanIN grade in WT mice. These results suggested that the expression of CRMP4 in stromal cells may underlie the incidence or progression of PanIN.
DOI	10.1016/j.tranon.2020.100746
PMID	32105991