CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb
Effective therapies have yet to be established for pancreatic ductal adenocarcinomas (PDAC) even though it is the most aggressive cancer. In the present study, PDAC was analyzed using novel rat mAbs against membrane proteins in conjunction with flow cytometry and immunohistochemistry. Human epiderma...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13963 |
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| author | Takashi Nakano Kouki Okita Shogo Okazaki Soshi Yoshimoto Sachiko Masuko Hideki Yagi Kazunori Kato Yoshihisa Tomioka Kenichi Imai Yoichi Hamada Kazue Masuko Kayoko Shimada‐Takaura Noriaki Nagai Hideyuki Saya Tomio Arai Toshiyuki Ishiwata Takashi Masuko |
| author_facet | Takashi Nakano Kouki Okita Shogo Okazaki Soshi Yoshimoto Sachiko Masuko Hideki Yagi Kazunori Kato Yoshihisa Tomioka Kenichi Imai Yoichi Hamada Kazue Masuko Kayoko Shimada‐Takaura Noriaki Nagai Hideyuki Saya Tomio Arai Toshiyuki Ishiwata Takashi Masuko |
| author_sort | Takashi Nakano |
| collection | DOAJ |
| description | Effective therapies have yet to be established for pancreatic ductal adenocarcinomas (PDAC) even though it is the most aggressive cancer. In the present study, PDAC was analyzed using novel rat mAbs against membrane proteins in conjunction with flow cytometry and immunohistochemistry. Human epidermal growth receptor (HER)1–4, mesenchymal to epithelial transition factor (MET), sphingosine‐1‐phospahate receptor 1 (S1PR1), l‐type amino acid transporter 1 (LAT1), system x−c transporter (xCT), alanine‐serine‐cysteine transporter (ASCT2), cationic amino acid transporter 1 (CAT1) and variant CD44 (CD44v) were expressed at high frequencies in both in vitro and in vivo PDAC. Internalization of membrane proteins by mAbs and growth inhibition by toxin‐linked mAbs were demonstrated in many PDAC cell lines, and mAbs against S1PR1, ASCT2, HER3 and CD44v inhibited the growth of xenografted MIA PaCa‐2 PDAC cells. Furthermore, CD44v‐high PDAC showed high mRNA expression of HER1–3, MET and CD44v, and was correlated with poor prognosis. Taken together, our results suggest that CD44v, S1PR1, HER3, MET and the above‐mentioned cancer‐associated amino acid transporters might be promising targets for the diagnosis and treatment of PDAC. |
| format | Article |
| id | doaj-art-9c4e55f65ffe463bbb4edc9c3119bf31 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-9c4e55f65ffe463bbb4edc9c3119bf312025-08-20T03:52:16ZengWileyFEBS Open Bio2211-54632025-05-0115586788410.1002/2211-5463.13963CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAbTakashi Nakano0Kouki Okita1Shogo Okazaki2Soshi Yoshimoto3Sachiko Masuko4Hideki Yagi5Kazunori Kato6Yoshihisa Tomioka7Kenichi Imai8Yoichi Hamada9Kazue Masuko10Kayoko Shimada‐Takaura11Noriaki Nagai12Hideyuki Saya13Tomio Arai14Toshiyuki Ishiwata15Takashi Masuko16Cell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanFaculty of Health and Sports Sciences Toyo University Kita‐ku JapanOncology Pharmacy Practice and Science, Graduate School of Pharmaceutical Sciences Tohoku University Sendai‐shi JapanDepartment of Microbiology, Division of Immunology and Pathobiology, School of Dentistry Nihon University Chiyoda‐ku JapanHamada Clinic Higashiosaka‐shi JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanNatural Drug Resources, Faculty of Pharmacy Kindai University Higashiosaka‐shi JapanAdvanced Design for Pharmaceuticals, School of Pharmacy Kindai University Higashiosaka‐shi JapanOncology Innovation Center Fujita Health University Toyoake‐shi JapanDivision of Aging and Carcinogenesis, Research Team for Geriatric Pathology Tokyo Metropolitan Institute for Geriatrics and Gerontology Itabashi‐ku JapanDivision of Aging and Carcinogenesis, Research Team for Geriatric Pathology Tokyo Metropolitan Institute for Geriatrics and Gerontology Itabashi‐ku JapanCell Biology Laboratory, School of Pharmacy Kindai University Higashiosaka‐shi JapanEffective therapies have yet to be established for pancreatic ductal adenocarcinomas (PDAC) even though it is the most aggressive cancer. In the present study, PDAC was analyzed using novel rat mAbs against membrane proteins in conjunction with flow cytometry and immunohistochemistry. Human epidermal growth receptor (HER)1–4, mesenchymal to epithelial transition factor (MET), sphingosine‐1‐phospahate receptor 1 (S1PR1), l‐type amino acid transporter 1 (LAT1), system x−c transporter (xCT), alanine‐serine‐cysteine transporter (ASCT2), cationic amino acid transporter 1 (CAT1) and variant CD44 (CD44v) were expressed at high frequencies in both in vitro and in vivo PDAC. Internalization of membrane proteins by mAbs and growth inhibition by toxin‐linked mAbs were demonstrated in many PDAC cell lines, and mAbs against S1PR1, ASCT2, HER3 and CD44v inhibited the growth of xenografted MIA PaCa‐2 PDAC cells. Furthermore, CD44v‐high PDAC showed high mRNA expression of HER1–3, MET and CD44v, and was correlated with poor prognosis. Taken together, our results suggest that CD44v, S1PR1, HER3, MET and the above‐mentioned cancer‐associated amino acid transporters might be promising targets for the diagnosis and treatment of PDAC.https://doi.org/10.1002/2211-5463.13963amino acid transporterCD44vHER3METpancreatic cancerS1PR1 |
| spellingShingle | Takashi Nakano Kouki Okita Shogo Okazaki Soshi Yoshimoto Sachiko Masuko Hideki Yagi Kazunori Kato Yoshihisa Tomioka Kenichi Imai Yoichi Hamada Kazue Masuko Kayoko Shimada‐Takaura Noriaki Nagai Hideyuki Saya Tomio Arai Toshiyuki Ishiwata Takashi Masuko CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb FEBS Open Bio amino acid transporter CD44v HER3 MET pancreatic cancer S1PR1 |
| title | CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb |
| title_full | CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb |
| title_fullStr | CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb |
| title_full_unstemmed | CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb |
| title_short | CD44v, S1PR1, HER3, MET and cancer‐associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb |
| title_sort | cd44v s1pr1 her3 met and cancer associated amino acid transporters are promising targets for the pancreatic cancers characterized using mab |
| topic | amino acid transporter CD44v HER3 MET pancreatic cancer S1PR1 |
| url | https://doi.org/10.1002/2211-5463.13963 |
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