ID 111126
Author
Tomida, Chisato University of Tokushima
Yamagishi, Naoko Wakayama Medical University
Nagano, Hikaru University of Tokushima
Ohno, Ayako University of Tokushima
Keywords
VEGF receptor tyrosine kinase inhibitor
sunitinib
evasive adaptation
Content Type
Journal Article
Description
Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possiblemechanisms for the adaptationmay be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activationin sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
64
Issue
3-4
Start Page
250
End Page
254
Sort Key
250
Published Date
2017-08
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences