Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model
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),...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-10-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4259 |
| _version_ | 1818742463377965056 |
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| author | Song‐Yi Lee Seonggyu Byeon Jihoon Ko Sujin Hyung In‐Kyoung Lee Noo Li Jeon Jung Yong Hong Seung Tae Kim Se Hoon Park Jeeyun Lee |
| author_facet | Song‐Yi Lee Seonggyu Byeon Jihoon Ko Sujin Hyung In‐Kyoung Lee Noo Li Jeon Jung Yong Hong Seung Tae Kim Se Hoon Park Jeeyun Lee |
| author_sort | Song‐Yi Lee |
| collection | DOAJ |
| description | 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‐β 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. |
| first_indexed | 2024-12-18T02:12:55Z |
| format | Article |
| id | doaj.art-2edd175f623c4b63bfcae52d114962bf |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-18T02:12:55Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-2edd175f623c4b63bfcae52d114962bf2022-12-21T21:24:27ZengWileyCancer Medicine2045-76342021-10-0110207253726210.1002/cam4.4259Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell modelSong‐Yi Lee0Seonggyu Byeon1Jihoon Ko2Sujin Hyung3In‐Kyoung Lee4Noo Li Jeon5Jung Yong Hong6Seung Tae Kim7Se Hoon Park8Jeeyun Lee9Division of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDepartment of Internal Medicine Chungbuk National University HospitalChungbuk National University College of Medicine Cheongju KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDepartment of Mechanical Engineering Seoul National University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaDivision of Hematology‐Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University Seoul KoreaAbstract 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‐β 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.https://doi.org/10.1002/cam4.4259angiogenesisepithelial–mesenchymal transition (EMT)gastric cancerramucirumab |
| spellingShingle | Song‐Yi Lee Seonggyu Byeon Jihoon Ko Sujin Hyung In‐Kyoung Lee Noo Li Jeon Jung Yong Hong Seung Tae Kim Se Hoon Park Jeeyun Lee Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model Cancer Medicine angiogenesis epithelial–mesenchymal transition (EMT) gastric cancer ramucirumab |
| title | Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model |
| title_full | Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model |
| title_fullStr | Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model |
| title_full_unstemmed | Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model |
| title_short | Reducing tumor invasiveness by ramucirumab and TGF‐β receptor kinase inhibitor in a diffuse‐type gastric cancer patient‐derived cell model |
| title_sort | reducing tumor invasiveness by ramucirumab and tgf β receptor kinase inhibitor in a diffuse type gastric cancer patient derived cell model |
| topic | angiogenesis epithelial–mesenchymal transition (EMT) gastric cancer ramucirumab |
| url | https://doi.org/10.1002/cam4.4259 |
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