Abstract
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 x 104 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-I 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.
| Original language | English |
|---|---|
| Pages (from-to) | 258-263 |
| Number of pages | 6 |
| Journal | International Journal of Cancer |
| Volume | 73 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1997 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Adenovirus-mediated gene transfer of fibroblast growth factor-1 : Angiogenesis and tumorigenicity in nude mice. / Pili, Roberto; Chang, Joan; Muhlhauser, Judith; Crystal, Ronald G.; Capogrossi, Maurizio C.; Passaniti, Antonino.
In: International Journal of Cancer, Vol. 73, No. 2, 1997, p. 258-263.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adenovirus-mediated gene transfer of fibroblast growth factor-1
T2 - Angiogenesis and tumorigenicity in nude mice
AU - Pili, Roberto
AU - Chang, Joan
AU - Muhlhauser, Judith
AU - Crystal, Ronald G.
AU - Capogrossi, Maurizio C.
AU - Passaniti, Antonino
PY - 1997
Y1 - 1997
N2 - 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 x 104 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-I 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.
AB - 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 x 104 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-I 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.
UR - http://www.scopus.com/inward/record.url?scp=0030768428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030768428&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19971009)73:2<258::AID-IJC16>3.0.CO;2-B
DO - 10.1002/(SICI)1097-0215(19971009)73:2<258::AID-IJC16>3.0.CO;2-B
M3 - Article
C2 - 9335452
AN - SCOPUS:0030768428
VL - 73
SP - 258
EP - 263
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -