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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/C749    most recent 00537.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Meng, F. Articles by Patel, T. Search for Related Content PubMed PubMed Citation Articles by Meng, F. Articles by Patel, T.

VASCULAR BIOLOGY

Chemotherapeutic stress selectively activates NF-B-dependent AKT and VEGF expression in liver cancer-derived endothelial cells

¹Department of Internal Medicine, Scott and White Clinic, Texas A&M University System Health Science Center College of Medicine, Temple, Texas; and ²Department of Internal Medicine, The Ohio State University, Columbus, Ohio

Submitted 18 October 2006 ; accepted in final form 29 May 2007

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-B-dependent angiogenesis was different between N-EC and T-EC. Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF-B-Akt-dependent manner. Both NF-B and Akt were involved in enhanced survival and migration in T-EC in response to chemotherapeutic stress. Moreover, Akt was involved in NF-B-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.

angiogenesis; hepatocellular cancer; inflammation; chemotherapy; transcription factor