We explored the effect of Noggin protein expression on tumor growth in vivo by using fluorescence imaging.
Human lung carcinoma MV522 cells were transduced by using bicistronic (EGFP/Nog) or a control (EGFP) lentivirus at >95% efficacy. The transduced cells were implanted in athymic mice either individually or after mixing with DsRed2-expressing MV522 cells.
The expression of Noggin protein was demonstrated in EGFP+/Nog+ but not in EGFP+ cell lysates and conditioned media. Noggin did not inhibit tumor cell proliferation in vitro. Implantation of EGFP+ resulted in rapid tumor growth, whereas mice implanted with EGFP+/Nog+ either failed to develop tumors or developed smaller slowly proliferating ones. In the case of tumors grown from mixtures with DsRed2+ cells, only Noggin-expressing cells resulted in decreased tumor volumes with low vascular density and poorly developed stroma.
The effect of Noggin protein expression is a consequence of inhibition of stromal and/or endothelial proliferation in vivo.
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This work was supported in part by RO1 EB000858 grant (A.B.). The authors are grateful to Dr. Miguel Esteves (Department of Neurology, UMASS Medical School) for providing high-titer lentiviral vectors for this study and to Dr. Mary Mazzanti for editing the text.
Conflicts of interest
The authors have no conflicts of interest.
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Kang, H., Gupta, S. & Bogdanov, A. Orthotopic Expression of Noggin Protein in Cancer Cells Inhibits Human Lung Carcinoma Growth In Vivo . Mol Imaging Biol 14, 480–488 (2012). https://doi.org/10.1007/s11307-011-0518-y
- Lung carcinoma