TY - JOUR
T1 - CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb
AU - Nakano, Takashi
AU - Okita, Kouki
AU - Okazaki, Shogo
AU - Yoshimoto, Soshi
AU - Masuko, Sachiko
AU - Yagi, Hideki
AU - Kato, Kazunori
AU - Tomioka, Yoshihisa
AU - Imai, Kenichi
AU - Hamada, Yoichi
AU - Masuko, Kazue
AU - Shimada-Takaura, Kayoko
AU - Nagai, Noriaki
AU - Saya, Hideyuki
AU - Arai, Tomio
AU - Ishiwata, Toshiyuki
AU - Masuko, Takashi
N1 - Publisher Copyright:
© 2025 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - amino acid transporter
KW - CD44v
KW - HER3
KW - MET
KW - pancreatic cancer
KW - S1PR1
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U2 - 10.1002/2211-5463.13963
DO - 10.1002/2211-5463.13963
M3 - Article
AN - SCOPUS:85214356331
SN - 2211-5463
JO - FEBS Open Bio
JF - FEBS Open Bio
ER -
