Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
01 Mar 2021
Historique:
received: 12 01 2021
revised: 19 02 2021
accepted: 24 02 2021
entrez: 3 4 2021
pubmed: 4 4 2021
medline: 28 4 2021
Statut: epublish

Résumé

Accumulating evidence indicates that an elevated ephrin-A1 expression is positively correlated with a worse prognosis in some cancers such as colon and liver cancer. The detailed mechanism of an elevated ephrin-A1 expression in a worse prognosis still remains to be fully elucidated. We previously reported that ADAM12-cleaved ephrin-A1 enhanced lung vascular permeability and thereby induced lung metastasis. However, it is still unclear whether or not cleaved forms of ephrin-A1 are derived from primary tumors and have biological activities. We identified the ADAM12-mediated cleavage site of ephrin-A1 by a Matrix-assisted laser desorption ionization mass spectrometry and checked levels of ephrin-A1 in the serum and the urine derived from the primary tumors by using a mouse model. We found elevated levels of tumor-derived ephrin-A1 in the serum and the urine in the tumor-bearing mice. Moreover, inhibition of ADAM-mediated cleavage of ephrin-A1 or antagonization of the EphA receptors resulted in a significant reduction of lung metastasis. The results suggest that tumor-derived ephrin-A1 is not only a potential biomarker to predict lung metastasis from the primary tumor highly expressing ephrin-A1 but also a therapeutic target of lung metastasis.

Identifiants

pubmed: 33804570
pii: ijms22052480
doi: 10.3390/ijms22052480
pmc: PMC7957476
pii:
doi:

Substances chimiques

Ephrin-A1 0
Receptor, EphA2 EC 2.7.10.1
ADAM12 Protein EC 3.4.24.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 25122716
Organisme : Japan Society for the Promotion of Science
ID : 25870760

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Auteurs

Katsuaki Ieguchi (K)

Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-karasuyama, Setagaya, Tokyo 157-8777, Japan.

Takeshi Tomita (T)

Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Department of Biochemistry and Molecular Biology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.

Toshifumi Takao (T)

Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 567-0871, Japan.

Tsutomu Omori (T)

Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.

Taishi Mishima (T)

Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.

Isao Shimizu (I)

Department of Applied Chemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo 169-8555, Japan.

Massimiliano Tognolini (M)

Department of Food and Drug, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.

Alessio Lodola (A)

Department of Food and Drug, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.

Takuya Tsunoda (T)

Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa, Tokyo 142-8555, Japan.

Shinichi Kobayashi (S)

Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-karasuyama, Setagaya, Tokyo 157-8777, Japan.

Satoshi Wada (S)

Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-karasuyama, Setagaya, Tokyo 157-8777, Japan.
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-karasuyama, Setagaya, Tokyo 157-8777, Japan.

Yoshiro Maru (Y)

Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.

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Classifications MeSH