Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
04 11 2021
Historique:
received: 23 01 2021
accepted: 20 09 2021
entrez: 5 11 2021
pubmed: 6 11 2021
medline: 27 1 2022
Statut: epublish

Résumé

L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients' survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.

Identifiants

pubmed: 34737339
doi: 10.1038/s41598-021-00811-8
pii: 10.1038/s41598-021-00811-8
pmc: PMC8569019
doi:

Substances chimiques

Amino Acid Transport System L 0
Amino Acid Transport Systems 0
Large Neutral Amino Acid-Transporter 1 0
SLC7A5 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

21638

Informations de copyright

© 2021. The Author(s).

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Auteurs

Narangerel Jigjidkhorloo (N)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Center of Hematology and Blood & Marrow Transplantation, The First Central Hospital of Mongolia, Ulaanbaatar, 14210, Mongolia.

Kohsuke Kanekura (K)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan. kanekura@tokyo-med.ac.jp.

Jun Matsubayashi (J)

Department of Anatomical Pathology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Daigo Akahane (D)

Department of Hematology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Koji Fujita (K)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Keiki Oikawa (K)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Atsushi Kurata (A)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Masakatsu Takanashi (M)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Hitoshi Endou (H)

J-Pharma Co., Ltd., 75-1 Ono-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0046, Japan.

Toshitaka Nagao (T)

Department of Anatomical Pathology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Akihiko Gotoh (A)

Department of Hematology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Oyundelger Norov (O)

Center of Hematology and Blood & Marrow Transplantation, The First Central Hospital of Mongolia, Ulaanbaatar, 14210, Mongolia.

Masahiko Kuroda (M)

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan. kuroda@tokyo-med.ac.jp.

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