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.