TY - JOUR
T1 - Chemotherapeutic stress selectively activates NF-κB-dependent AKT and VEGF expression in liver cancer-derived endothelial cells
AU - Meng, Fanyin
AU - Henson, Roger
AU - Patel, Tushar
PY - 2007/8
Y1 - 2007/8
N2 - Targeting endothelial cells (EC) that line tumor blood vessels forms the basis for metronomic therapy and is a promising new strategy for the treatment of cancer. Genetic and phenotypic differences between tumor-derived and normal ECs indicate that targeting tumor ECs may be therapeutically useful. In the present study, we examined differences in responses to chemotherapy in microvascular EC lines from tumoral (T-EC) and normal (N-EC) mouse liver tissues. The identity of these cells was confirmed by immunocytochemistry for EC markers, such as vascular endothelial-cadherin and CD31 for both types of ECs, and the tumor-endothelial-specific marker tumor endothelial marker-7 for T-EC. The involvement of Akt in NF-κB-dependent angiogenesis was different between N-EC and T-EC. Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF-κB-Akt-dependent manner. Both NF-κB and Akt were involved in enhanced survival and migration in T-EC in response to chemotherapeutic stress. Moreover, Akt was involved in NF-κB-dependent VEGF expression and angiogenesis. These studies, showing differences in cellular responses to chemotherapy in tumor-derived ECs, indicate that specific therapies targeting these cells may be therapeutically useful for liver cancers.
AB - Targeting endothelial cells (EC) that line tumor blood vessels forms the basis for metronomic therapy and is a promising new strategy for the treatment of cancer. Genetic and phenotypic differences between tumor-derived and normal ECs indicate that targeting tumor ECs may be therapeutically useful. In the present study, we examined differences in responses to chemotherapy in microvascular EC lines from tumoral (T-EC) and normal (N-EC) mouse liver tissues. The identity of these cells was confirmed by immunocytochemistry for EC markers, such as vascular endothelial-cadherin and CD31 for both types of ECs, and the tumor-endothelial-specific marker tumor endothelial marker-7 for T-EC. The involvement of Akt in NF-κB-dependent angiogenesis was different between N-EC and T-EC. Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF-κB-Akt-dependent manner. Both NF-κB and Akt were involved in enhanced survival and migration in T-EC in response to chemotherapeutic stress. Moreover, Akt was involved in NF-κB-dependent VEGF expression and angiogenesis. These studies, showing differences in cellular responses to chemotherapy in tumor-derived ECs, indicate that specific therapies targeting these cells may be therapeutically useful for liver cancers.
KW - Angiogenesis
KW - Chemotherapy
KW - Hepatocellular cancer
KW - Inflammation
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=34547790207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547790207&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00537.2006
DO - 10.1152/ajpcell.00537.2006
M3 - Article
C2 - 17537803
AN - SCOPUS:34547790207
SN - 0363-6143
VL - 293
SP - C749-C760
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2
ER -