Inhibition of cyclo-oxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor
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* Corresponding author: Jason C Fisher Jason.Fisher@cchmc.org
- Equal contributors
1 Department of Surgery, Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave, Cincinnati, 45229-3039, USA
2 Department of Surgery, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, New York 10032, USA
3 Department of Pathology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, New York 10032, USA
4 Department of Pediatrics, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, New York 10032, USA
5 Center for Computational Biology and Bioinformatics, College of Physicians and Surgeons of Columbia University, 1130 St. Nicholas Ave, New York, New York 10032, USA
Vascular Cell 2011, 3:22 doi:10.1186/2045-824X-3-22
Published: 6 October 2011Additional files
Additional file 1:
Table S1. LimmaAnnotated.xls: Differential gene expression was computed using an Empirical Bayesian model implemented in the Limma package. Briefly, we analyzed microarray data obtained using HG-U133A GeneChips (Affymetrix, Santa Clara, CA) to investigate gene expression in xenografts. Raw CEL files were processed using Bioconductor packages in an R environment http://www.bioconductor.org webcite). Quality controls were performed by inspecting Affymetrix® metrics using the simpleaffy package. Probe level signals were then background-corrected, normalized, and summarized using the GC-RMA function, and differential gene expression then computed as above.
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Additional file 2:
Figure S1. Metastases in combination SC236 and BV-treated mouse lungs appeared smaller than in control or single-agent treated animals. The low incidence of metastasis in this group (2/15) prevented quantitation of this size reduction, although it may reflect decreased efficiency of metastasis in this group.
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Additional file 3:
Figure S2. The addition of SC236 does not alter expression of lung metastasis signature genes during VEGF blockade. We examined expression of 7 genes (COL6A1, CSF2RA, CXCR4, KRT81, MATN2, SPARC, TNC) included in the lung metastasis gene signature described by Minn et al. (8) in tumor extracts from each group (N = 6, controls, SC236-treated, BV-treated; N = 5, BV+SC236 treated). Comparison was performed by real-time PCR. No significant differences between BV and SC236+BV treated tumors were found, suggesting that SC236 did not reduce lung metastasis by suppressing expression of these genes.
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