These authors contributed equally to this study.
Melanoma-derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature
Article first published online: 19 JUN 2012
© 2012 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 25, Issue 4, pages 493–505, July 2012
How to Cite
Wang, T., Ge, Y., Xiao, M., Lopez-Coral, A., Azuma, R., Somasundaram, R., Zhang, G., Wei, Z., Xu, X., Rauscher, F. J., Herlyn, M. and Kaufman, R. E. (2012), Melanoma-derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature. Pigment Cell & Melanoma Research, 25: 493–505. doi: 10.1111/j.1755-148X.2012.01005.x
- Issue published online: 19 JUN 2012
- Article first published online: 19 JUN 2012
- Accepted manuscript online: 12 APR 2012 01:38PM EST
- PUBLICATION DATA Received 7 March 2012, revised and accepted for publication 9 April 2012, published online 12 April 2012
- tumor microenvironment;
- glycoprotein non-metastatic melanoma protein B
The presence of tumor-associated macrophages (TAMs) in melanomas is correlated with a poor clinical prognosis. However, there is limited information on the characteristics and biological activities of human TAMs in melanomas. In this study, we developed an in vitro method to differentiate human monocytes to macrophages using modified melanoma-conditioned medium (MCM). We demonstrate that factors from MCM-induced macrophages (MCMI-Mφ) express both M1-Mφ and M2-Mφ markers and inhibit melanoma-specific T-cell proliferation. Furthermore, microarray analyses reveal that the majority of genes up-regulated in MCMI-Mφ are associated with tumor invasion. The most strikingly up-regulated genes are CCL2 and MMP-9. Consistent with this, blockade of both CCL-2 and MMPs diminish MCMI-Mφ-induced melanoma invasion. Finally, we demonstrated that both MCMI-Mφ and in vivo TAMs express the pro-invasive, melanoma-associated gene, glycoprotein non-metastatic melanoma protein B. Our study provides a framework for understanding the mechanisms of cross-talk between TAMs and melanoma cells within the tumor microenvironment.