CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial-Mesenchymal Transition

The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (E...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2023-03, Vol.15 (6), p.1878
Main Authors: Oba, Mitsunobu, Nakanishi, Yoshitsugu, Mitsuhashi, Tomoko, Sasaki, Katsunori, Hatanaka, Kanako C, Sasaki, Masako, Nange, Ayae, Okumura, Asami, Hayashi, Mariko, Yoshida, Yusuke, Nitta, Takeo, Ueno, Takashi, Yamada, Toru, Ono, Masato, Kuwabara, Shota, Okamura, Keisuke, Tsuchikawa, Takahiro, Nakamura, Toru, Noji, Takehiro, Asano, Toshimichi, Tanaka, Kimitaka, Takayama, Kiyoshi, Hatanaka, Yutaka, Hirano, Satoshi
Format: Article
Language:English
Subjects:
Antigens
Bile ducts
Cancer
CC chemokine receptors
CCL19 protein
CCR7 protein
Cell differentiation
Cell migration
Cell receptors
Chemokine receptors
Chemokines
Cholangiocarcinoma
E-cadherin
Health aspects
Lymphatic system
Medical prognosis
Medical research
Metastases
Metastasis
Molecular modelling
Physiology
Review boards
Tumors
Vimentin
Western blotting
Wound healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15061878