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Cancer Lett. 2014 Apr 28;346(1):45-52. doi: 10.1016/j.canlet.2013.12.004. Epub 2013 Dec 11.

Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression.

Author information

1
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
2
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: jfang@tongji.edu.cn.

Abstract

Increasing evidence has indicated that prolonged use of anti-VEGF (vascular endothelial growth factor) agents for cancer therapy promotes tumor resistance. To gain insight into the molecular mechanism underlying resistance to anti-VEGF therapy, we developed a mouse Lewis lung carcinoma (LLC) cell line that is resistant to treatment with a potent VEGF inhibitor, VEGF-Trap, through repeated in vivo selection. We compared the transcriptome profiles of resistant and non-resistant tumor cells using RNA-seq analysis. VEGF-C was significantly up-regulated in resistant tumor cells, as determined by quantitative real-time PCR and immunohistochemical analyses. Inhibition of VEGF-C in resistant cells suppressed endothelial cell migration in vitro and partially restored sensitivity to VEGF-Trap treatment in vivo. Our findings indicate that tumors may develop resistance to anti-VEGF therapy by activating the VEGF-C pathway.

KEYWORDS:

Angiogenesis; Animal model; Drug resistance; Lung carcinoma; RNA-seq; VEGF

PMID:
24333721
DOI:
10.1016/j.canlet.2013.12.004
[Indexed for MEDLINE]

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