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Adenovirus‐mediated gene transfer of fibroblast growth factor‐1: Angiogenesis and tumorigenicity in nude mice
Author(s) -
Pili Roberto,
Chang Joan,
Muhlhauser Judith,
Crystal Ronald G.,
Capogrossi Maurizio C.,
Passaniti Antonino
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971009)73:2<258::aid-ijc16>3.0.co;2-b
Subject(s) - angiogenesis , gene transfer , cancer research , basic fibroblast growth factor , fibroblast growth factor , fibroblast , biology , genetic enhancement , adenoviridae , gene , growth factor , virology , cell culture , genetics , receptor
Gene transfer of angiogenic growth factors with replication‐deficient recombinant adenovirus (Ad) vectors may provide a new approach to the treatment of ischemic diseases. To determine if Ad‐infected cells could stimulate angiogenesis in vivo and to assess the tumorigenicity of cells infected with these vectors, NIH3T3 fibroblasts infected with Ad vectors coding for human acidic fibroblast growth factor (aFGF‐1) were used in angiogenic and tumorigenic assays. Infected cells induced a strong angiogenic response in vivo, while cells infected with control virus did not. Stable 3T3 transfectants expressing the FGF ‐1 gene were also highly angiogenic and exhibited growth in soft agar, while Ad‐infected cells did not. Ad‐infected cells grew transiently in nude mice, whereas 3T3 transfectants formed large tumors which grew exponentially. Extrapolation of cell dose‐response curves showed that a minimum of 1.5 × 10 4 infected cells were required for transient tumor cell growth in vivo. Ad‐infected cells cultured in vitro for 30 days lost their invasive phenotype and the ability for transient cell growth in nude mice. Thus, phenotypic changes induced by Ad‐mediated gene transfer of FGF ‐1 are transient both in vitro and in vivo, suggesting that these Ad vectors do not have tumorigenic potential. Stimulation of angiogenesis by Ad‐infected cells may be useful for the evaluation of anti‐angiogenic and anti‐tumor agents. Int. J. Cancer 73:258–263, 1997. Published 1997 Wiley‐Liss, Inc.