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

Tao Wang, Yingbin Ge, Min Xiao, Alfonso Lopez-Coral, Rikka Azuma, Rajasekharan Somasundaram, Gao Zhang, Zhi Wei, Xiaowei Xu, Frank J. Rauscher, Meenhard Herlyn, Russel E. Kaufman

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)493-505
Number of pages13
JournalPigment Cell and Melanoma Research
Volume25
Issue number4
DOIs
StatePublished - Jul 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

Keywords

  • Glycoprotein non-metastatic melanoma protein B
  • Invasion
  • Macrophages
  • Melanoma
  • Tumor microenvironment

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