ORIGINAL ARTICLE

Melanoma-derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature

  1. Tao Wang1,†,
  2. Yingbin Ge1,2,†,
  3. Min Xiao1,
  4. Alfonso Lopez-Coral1,3,
  5. Rikka Azuma4,
  6. Rajasekharan Somasundaram1,
  7. Gao Zhang1,
  8. Zhi Wei5,
  9. Xiaowei Xu6,
  10. Frank J. Rauscher III7,
  11. Meenhard Herlyn1,
  12. Russel E. Kaufman1

Article first published online: 19 JUN 2012

DOI: 10.1111/j.1755-148X.2012.01005.x

Issue

Pigment Cell & Melanoma Research

Pigment Cell & Melanoma Research

Volume 25, Issue 4, pages 493–505, July 2012

Additional Information

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

Author Information

  1. 1

     Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA

  2. 2

     Department of Physiology, Nanjing Medical University, Nanjing, China

  3. 3

     Graduate Program, The Catholic University of America, Washington, DC, USA

  4. 4

     Undergraduate Program

  5. 5

     Department of Computer Science, New Jersey Institute of Technology

  6. 6

     Department of Pathology and Laboratory Medicine, University of Pennsylvania

  7. 7

     Gene Expression and Regulation Program, The Wistar Institute

  1. †

    These authors contributed equally to this study.

*Tao Wang, e-mail: twang@wistar.org and Russel E. Kaufman, e-mail: kaufman@wistar.org

  1. †

    These authors contributed equally to this study.

Publication History

  1. Issue published online: 19 JUN 2012
  2. Article first published online: 19 JUN 2012
  3. Accepted manuscript online: 12 APR 2012 01:38PM EST
  4. PUBLICATION DATA Received 7 March 2012, revised and accepted for publication 9 April 2012, published online 12 April 2012

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Keywords:

  • melanoma;
  • macrophages;
  • invasion;
  • tumor microenvironment;
  • glycoprotein non-metastatic melanoma protein B

Summary

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.

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