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Orthotopic Expression of Noggin Protein in Cancer Cells Inhibits Human Lung Carcinoma Growth In Vivo

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.

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Acknowledgment

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.

Author information

Correspondence to Alexei Bogdanov Jr..

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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

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Key words

  • Noggin
  • BMP
  • Fluorescence
  • Cancer
  • Stroma
  • Xenograft
  • Lung carcinoma