Reducing tumor invasiveness by ramucirumab and TGF-beta receptor kinase inhibitor in a diffuse-type gastric cancer patient-derived cell modelopen access
- Authors
- Lee, Song-Yi; Byeon, Seonggyu; Ko, Jihoon; Hyung, Sujin; Lee, In-Kyoung; Li Jeon, Noo; Hong, Jung Yong; Kim, Seung Tae; Park, Se Hoon; Lee, Jeeyun
- Issue Date
- Oct-2021
- Publisher
- WILEY
- Keywords
- angiogenesis; epithelial-mesenchymal transition (EMT); gastric cancer; ramucirumab
- Citation
- CANCER MEDICINE, v.10, no.20, pp.7253 - 7262
- Journal Title
- CANCER MEDICINE
- Volume
- 10
- Number
- 20
- Start Page
- 7253
- End Page
- 7262
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/87312
- DOI
- 10.1002/cam4.4259
- ISSN
- 2045-7634
- Abstract
- Background Diffuse-type gastric cancer (GC) is known to be more aggressive and relatively resistant to conventional chemotherapy. Hence, more optimized treatment strategy is urgently needed in diffuse-type GC. Methods Using a panel of 10 GC cell lines and 3 GC patient-derived cells (PDCs), we identified cell lines with high EMTness which is a distinct feature for diffuse-type GC. We treated GC cells with high EMTness with ramucirumab alone, TGF-beta receptor kinase inhibitor (TEW-7197) alone, or in combination to investigate the drug's effects on invasiveness, spheroid formation, EMT marker expression, and tumor-induced angiogenesis using a spheroid-on-a-chip model. Results Both TEW-7197 and ramucirumab treatments profoundly decreased invasiveness of EMT-high cell lines and PDCs. With a 3D tumor spheroid-on-a-chip, we identified versatile influence of co-treatment on cancer cell-induced blood vessel formation as well as on EMT progression in tumor spheroids. The 3D tumor spheroid-on-a-chip demonstrated that TEW-7197 + ramucirumab combination significantly decreased PDC-induced vessel formation. Conclusions In this study, we showed TEW-7197 and ramucirumab considerably decreased invasiveness, thus EMTness in a panel of diffuse-type GC cell lines including GC PDCs. Taken together, we confirmed that combination of TEW-7197 and ramucirumab reduced tumor spheroid and GC PDC-induced blood vessel formation concomitantly in the spheroid-on-a-chip model.
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