Inhibition of orthotopic human bladder tumor growth by lentiviral gene transfer of endostatin Journal Article
| Authors: | Kikuchi, E.; Menendez, S.; Ohori, M.; Cordon-Cardo, C.; Kasahara, N.; Bochner, B. H. |
| Article Title: | Inhibition of orthotopic human bladder tumor growth by lentiviral gene transfer of endostatin |
| Abstract: | Purpose: Inhibitors of endothelial cell proliferation, such as endostatin, result in suppression of tumor-associated angiogenesis and can achieve growth-inhibitory effects depending on the type of tumor treated. The purpose of this study was to investigate whether local overexpression of endostatin could serve to diminish tumor growth of bladder cancer in vivo. Experimental Design: We examined the capability of lentiviral-mediated gene transfer in vitro and therapeutic effects of lentivirus-based vectors expressing endostatin on tumor growth using an orthotopic human bladder tumor model. Results: We found that self-inactivating lentivirus vectors containing green fluorescent protein, alone or in combination with endostatin, were capable of efficient and stable gene transfer to a variety of human bladder tumor cell lines. The production and secretion of endostatin from lentivirus-transduced KU-7 human bladder cancer cells was confirmed by Western blot and competitive enzyme immunoassay. Intravesical instillation of untransduced, green fluorescent protein control lentivirus-transduced, and endostatin-transduced KU-7 cells was performed in murine models to establish orthotopic tumors. Sustained long-term expression of endostatin was achieved in lentivirus-transduced orthotopic bladder tumors, and it was associated with decreased vascularization and inhibition of tumor growth. Lentivirus vector-mediated overexpression of endostatin did not affect the intrinsic production of basic fibroblast growth factor and vascular endothelial growth factor. Conclusions: These findings suggest that lentivirus-mediated gene transfer might represent an effective strategy for expression of angioinhibitory peptides to achieve inhibition of human bladder cancer proliferation and tumor progression. |
| Keywords: | immunohistochemistry; vasculotropin; controlled study; protein expression; human cell; nonhuman; cell proliferation; mouse; animals; mice; animal tissue; cell division; green fluorescent protein; animal experiment; animal model; drug effect; drug screening; cell line, tumor; vascularization; bladder cancer; bladder tumor; urinary bladder neoplasms; gene transfer; genetic vectors; luminescent proteins; enzyme immunoassay; cancer inhibition; kinetics; recombinant fusion proteins; mice, nude; protein synthesis; cancer cell; western blotting; lentivirus; lentivirus vector; transplantation, heterologous; protein secretion; green fluorescent proteins; tumor growth; antiangiogenic activity; lentivirinae; gene transfer techniques; virus gene; basic fibroblast growth factor; endostatin; orthotopic transplantation; humans; human; female; priority journal; article; endostatins |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 5 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-03-01 |
| Start Page: | 1835 |
| End Page: | 1842 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-03-0099 |
| PROVIDER: | scopus |
| PUBMED: | 15014038 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):26 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
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11Kikuchi -
612
Cordon-Cardo -
50
Ohori -
468Bochner -
34
Menendez
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