| Title: | CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial-Mesenchymal Transition |
| Authors: | Oba, Mitsunobu Browse this author |
| Nakanishi, Yoshitsugu Browse this author →KAKEN DB |
| Mitsuhashi, Tomoko Browse this author |
| Sasaki, Katsunori Browse this author |
| Hatanaka, Kanako C. Browse this author |
| Sasaki, Masako Browse this author |
| Nange, Ayae Browse this author |
| Okumura, Asami Browse this author |
| Hayashi, Mariko Browse this author |
| Yoshida, Yusuke Browse this author |
| Nitta, Takeo Browse this author |
| Ueno, Takashi Browse this author |
| Yamada, Toru Browse this author |
| Ono, Masato Browse this author |
| Kuwabara, Shota Browse this author |
| Okamura, Keisuke Browse this author |
| Tsuchikawa, Takahiro Browse this author |
| Nakamura, Toru Browse this author |
| Noji, Takehiro Browse this author |
| Asano, Toshimichi Browse this author |
| Tanaka, Kimitaka Browse this author |
| Takayama, Kiyoshi Browse this author |
| Hatanaka, Yutaka Browse this author |
| Hirano, Satoshi Browse this author →KAKEN DB |
| Keywords: | CCR7 |
| CCL19 |
| extrahepatic cholangiocarcinoma |
| epithelial-mesenchymal transition |
| tumor budding |
| Issue Date: | Mar-2023 |
| Publisher: | MDPI |
| Journal Title: | Cancers |
| Volume: | 15 |
| Issue: | 6 |
| Start Page: | 1878 |
| Publisher DOI: | 10.3390/cancers15061878 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89272 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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