SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2-overexpressing human ovarian cancer
Journal
Cancer Gene Therapy
Journal Volume
18
Journal Issue
12
Pages
859-870
Date Issued
2011
Author(s)
Hsueh S.-P.
Hsu W.-B.
Wen C.-C.
WON-BO WANG
Abstract
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in human ovarian cancers and its overexpression is associated with increased angiogenesis, increased metastasis and reduced survival. Inhibition of HER2 in HER2-overexpressing cancers can lead to reduced angiogenesis and improved survival. Previously, we reported that SV40 T/t-common polypeptide has transcriptional repression activity and can inhibit HER2 expression. In this study, we investigated the effect of T/t-common on the angiogenesis-inducing activity of HER2-overexpressing human SK-OV-3 ovarian cancer cells. We found that compared to conditioned medium from control SK-OV-3 cancer cells, conditioned medium from T/t-common-expressing SK-OV-3 cells had a reduced ability to induce endothelial cell migration and tube formation in vitro and microvessel formation in vivo. These data indicate that T/t-common can inhibit the ability of SK-OV-3 cancer cells to induce angiogenesis. T/t-common was found to be able to downregulate the expression of several proangiogenic factors, including vascular endothelial growth factor-A, interleukin-8, basic fibroblast growth factor, matrix metalloproteinase-2 and urokinase-type plasminogen activator, and upregulate antiangiogenic factors, including thrombospondin-1 and tissue inhibitor of metalloproteinases-1 in SK-OV-3 cancer cells. Finally, we demonstrated that T/t-common could inhibit the angiogenesis and growth of HER2-overexpressing human ovarian tumor in NOD/SCID mice. Taken together, the data suggest that T/t-common had the potential to be developed as a new antiangiogenic agent specific for treating HER2-overexpressing ovarian cancers. ? 2011 Nature America, Inc. All rights reserved.
Subjects
angiogenesis; HER2; ovarian cancer; SV40 T/t-common; TSP-1; VEGF-A
Other Subjects
antineoplastic agent; epidermal growth factor receptor 2; fibroblast growth factor 2; gelatinase A; interleukin 8; plasminogen activator; sv40 T t common polypeptide; thrombospondin 1; tissue inhibitor of metalloproteinase 1; unclassified drug; vasculotropin A; Adenovirus; angiogenesis; animal experiment; animal model; animal tissue; article; cancer cell; cancer inhibition; cell migration; controlled study; endothelium cell; female; gene overexpression; human; human cell; in vitro study; in vivo study; mouse; nonhuman; ovary cancer; priority journal; upregulation; Animals; Antigens, Polyomavirus Transforming; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Culture Media, Conditioned; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Inbred NOD; Neovascularization, Pathologic; Ovarian Neoplasms; Peptides; Receptor, erbB-2; Mus
Type
journal article