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Melanoma‐derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature
Author(s) -
Wang Tao,
Ge Yingbin,
Xiao Min,
LopezCoral Alfonso,
Azuma Rikka,
Somasundaram Rajasekharan,
Zhang Gao,
Wei Zhi,
Xu Xiaowei,
Rauscher Frank J.,
Herlyn Meenhard,
Kaufman Russel E.
Publication year - 2012
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2012.01005.x
Subject(s) - melanoma , cancer research , in vitro , biology , gene signature , in vivo , macrophage , gene , immunology , gene expression , genetics
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.