Autor: |
Yomogi Shiota (Sato), Mohamed Elbadawy, Kazuhiko Suzuki, Ryouichi Tsunedomi, Hiroaki Nagano, Yusuke Ishihara, Haru Yamamoto, Daigo Azakami, Tsuyoshi Uchide, Ryuji Fukushima, Ryo Tanaka, Tomohiko Yoshida, Takuya Mori, Amira Abugomaa, Masahiro Kaneda, Hideyuki Yamawaki, Yuta Shinohara, Mohamed Aboubakr, Mohamed E. El-Asrag, Tatsuya Usui, Kazuaki Sasaki |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
|
Zdroj: |
Biomedicine & Pharmacotherapy, Vol 165, Iss , Pp 115079- (2023) |
Druh dokumentu: |
article |
ISSN: |
0753-3322 |
DOI: |
10.1016/j.biopha.2023.115079 |
Popis: |
Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|