In vivo gene transfer of pigment epithelium-derived factor inhibits tumor growth in syngeneic murine models of thoracic malignancies Journal Article
| Authors: | Mahtabifard, A.; Merritt, R. E.; Yamada, R. E.; Crystal, R. G.; Korst, R. J. |
| Article Title: | In vivo gene transfer of pigment epithelium-derived factor inhibits tumor growth in syngeneic murine models of thoracic malignancies |
| Abstract: | Objective: Pigment epithelium-derived factor is known to be an inhibitor of angiogenesis. We hypothesized that in vivo gene transfer of pigment epithelium-derived factor may inhibit tumor angiogenesis and growth in syngeneic models of thoracic malignancies. Methods: An adenovirus vector encoding the human pigment epithelium-derived factor cDNA (AdPEDF) was used to transduce human lung cancer cells in vitro. Transgene expression was assessed using Western analysis. Three different murine flank tumors (2 lung, 1 colon) were then established in syngeneic mice and treated intratumorally with phosphate-buffered saline, AdPEDF, or an empty vector (Ad-Null). Endpoints measured included transgene expression, tumor size, and animal survival, as well as microvessel density within the tumor. Additionally, a murine pulmonary metastasis model was established by intravenous injection of a syngeneic colon adenocarcinoma cell line expressing a marker gene (β-galactosidase). One day later, treatment (phosphate-buffered saline, AdNull, or AdPEDF) was administered intrapleurally. Tumor burden (gross and histologic inspection, lung weight, and β-galactosidase expression) was then evaluated 13 days after vector dosing, and survival was recorded. Results: AdPEDF-derived expression of pigment epithelium-derived factor was demonstrated in vitro and in vivo. In syngeneic murine lung cancer flank tumors, intratumoral administration of AdPEDF significantly inhibited tumor growth (P < .01), prolonged mouse survival (P < .01), and decreased microvessel density (P < .01) compared with control groups. In the pulmonary metastasis model, AdPEDF-treated mice exhibited significantly reduced lung lesions, lung weight (P < .0005), β-galactosidase expression (P < .05), and animal survival was prolonged (P < .05). Conclusion: Gene transfer of pigment epithelium-derived factor suppresses tumor vascularization and growth, while prolonging survival in syngeneic murine models of thoracic malignancies. |
| Keywords: | cancer survival; controlled study; survival analysis; human cell; histopathology; carcinoma, squamous cell; cancer growth; nonhuman; proteins; animal cell; mouse; animals; mice; gene expression; embryo; lung neoplasms; animal experiment; animal model; lung cancer; pigment epithelium derived factor; in vivo study; eye proteins; nerve growth factors; serpins; cancer cell culture; in vitro study; tumor cells, cultured; angiogenesis; mice, inbred balb c; mice, inbred c57bl; gene transfer; genetic vectors; thoracic neoplasms; western blotting; transgene; beta galactosidase; protein biosynthesis; adenovirus vector; disease models, animal; microvasculature; marker gene; injections, intravenous; gene transfer techniques; pigment epithelium; mice, inbred dba; lung weight; adenoviruses, human; models, cardiovascular; human; male; female; priority journal; article |
| Journal Title: | Journal of Thoracic and Cardiovascular Surgery |
| Volume: | 126 |
| Issue: | 1 |
| ISSN: | 0022-5223 |
| Publisher: | Mosby Elsevier |
| Date Published: | 2003-07-01 |
| Start Page: | 28 |
| End Page: | 38 |
| Language: | English |
| DOI: | 10.1016/s0022-5223(02)73616-7 |
| PUBMED: | 12878936 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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