Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.
ADAM
Eph
MMP
biomarker
cancer
ephrin
metastasis
poor prognosis
urinalysis
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
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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