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

Oba, Mitsunobu; Nakanishi, Yoshitsugu; Mitsuhashi, Tomoko et al.

Cancers, 2023, 15(6), 1878

Permalink : https://hdl.handle.net/2115/89272

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https://doi.org/10.3390/cancers15061878     1

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アクセス権
metadata only access
URI
https://hdl.handle.net/2115/89272
タイトル
CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial-Mesenchymal Transition
著者
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
著者名
Oba, Mitsunobu
e-Rad_Researcher
40447058
著者名
Nakanishi, Yoshitsugu
著者名
Mitsuhashi, Tomoko
著者名
Sasaki, Katsunori
著者名
Hatanaka, Kanako C.
著者名
Sasaki, Masako
著者名
Nange, Ayae
著者名
Okumura, Asami
著者名
Hayashi, Mariko
著者名
Yoshida, Yusuke
著者名
Nitta, Takeo
著者名
Ueno, Takashi
著者名
Yamada, Toru
著者名
Ono, Masato
著者名
Kuwabara, Shota
著者名
Okamura, Keisuke
著者名
Tsuchikawa, Takahiro
著者名
Nakamura, Toru
著者名
Noji, Takehiro
著者名
Asano, Toshimichi
著者名
Tanaka, Kimitaka
著者名
Takayama, Kiyoshi
著者名
Hatanaka, Yutaka
e-Rad_Researcher
50322813
著者名
Hirano, Satoshi
言語
英語
キーワード
CCR7
CCL19
extrahepatic cholangiocarcinoma
epithelial-mesenchymal transition
tumor budding
発行日
2023-03
出版者
MDPI
収録物名
Cancers
巻(号)
15(6)
ページ
1878
抄録
Simple Summary Extrahepatic cholangiocarcinoma (EHCC) is an aggressive tumor. The five-year survival rate for patients who undergo surgical resection is only 20-40% due to recurrences. Therefore, elucidating the molecular mechanisms underlying invasion and metastasis in EHCC is crucial for developing adjuvant therapy. 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. 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 two EHCC cell lines. CCR7 mediates cell invasion and migration in EHCC by inducing EMT, which was abrogated by a CCR7 antagonist. CCR7 may be a potential target for adjuvant therapy in EHCC. 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.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3390/cancers15061878