Orthotopic expression of noggin protein in cancer cells inhibits human lung carcinoma growth in vivo
Kang, Hye won ; Gupta, Suresh ; Bogdanov, Alexei A. Jr.
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UMass Chan Affiliations
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Keywords
Carrier Proteins
Cell Extracts
Cell Line, Tumor
Cell Proliferation
Culture Media, Conditioned
Fluorescence
Green Fluorescent Proteins
Humans
Immunoblotting
Immunohistochemistry
Lung Neoplasms
Mice
Mice, Nude
Molecular Imaging
Transduction, Genetic
*Xenograft Model Antitumor Assays
Amino Acids, Peptides, and Proteins
Cancer Biology
Investigative Techniques
Neoplasms
Radiology
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Abstract
PURPOSE: We explored the effect of Noggin protein expression on tumor growth in vivo by using fluorescence imaging.
PROCEDURES: 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.
RESULTS: 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.
CONCLUSION: The effect of Noggin protein expression is a consequence of inhibition of stromal and/or endothelial proliferation in vivo.
Source
Mol Imaging Biol. 2012 Aug;14(4):480-8. doi: 10.1007/s11307-011-0518-y. Link to article on publisher's site