ID 111128
著者
Tomida, Chisato University of Tokushima
Nagano, Hikaru University of Tokushima
Yamagishi, Naoko Wakayama Medical University
Ohno, Ayako University of Tokushima
キーワード
angiogenesis inhibitor
regorafenib
VEGF-R
tumor cell aggressiveness
資料タイプ
学術雑誌論文
抄録
Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenibtargeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
64
3-4
開始ページ
262
終了ページ
265
並び順
262
発行日
2017-08
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系