CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb

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

doi:10.1002/2211-5463.13963

CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb

FEBS Open Bio. 2025 Jan 5. doi: 10.1002/2211-5463.13963. Online ahead of print.

Authors

Takashi Nakano^{1

2}, Kouki Okita^{1

3}, Shogo Okazaki^{1

4}, Soshi Yoshimoto^{1

5}, Sachiko Masuko^{1

5}, Hideki Yagi^{1

6}, Kazunori Kato², Yoshihisa Tomioka⁷, Kenichi Imai⁴, Yoichi Hamada⁸, Kazue Masuko¹, Kayoko Shimada-Takaura⁹, Noriaki Nagai³, Hideyuki Saya¹⁰, Tomio Arai¹¹, Toshiyuki Ishiwata¹¹, Takashi Masuko^{1

3

10}

Affiliations

¹ Cell Biology Laboratory, School of Pharmacy, Kindai University, Higashiosaka-shi, Japan.
² Faculty of Health and Sports Sciences, Toyo University, Kita-ku, Japan.
³ Advanced Design for Pharmaceuticals, School of Pharmacy, Kindai University, Higashiosaka-shi, Japan.
⁴ Department of Microbiology, Division of Immunology and Pathobiology, School of Dentistry, Nihon University, Chiyoda-ku, Japan.
⁵ PIERAS Co., Ltd, Osaka-shi, Japan.
⁶ Department of Pharmaceuticals, Faculty of Pharmacy, International University of Health and Welfare, Otawara-shi, Japan.
⁷ Oncology Pharmacy Practice and Science, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai-shi, Japan.
⁸ Hamada Clinic, Higashiosaka-shi, Japan.
⁹ Natural Drug Resources, Faculty of Pharmacy, Kindai University, Higashiosaka-shi, Japan.
¹⁰ Oncology Innovation Center, Fujita Health University, Toyoake-shi, Japan.
¹¹ Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi-ku, Japan.

PMID: 39757718
DOI: 10.1002/2211-5463.13963

Abstract

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.

Keywords: CD44v; HER3; MET; S1PR1; amino acid transporter; pancreatic cancer.

Grants and funding

18H05463/MEXT/JSPS KAKENHI