title: Melanoma-derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature.
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.
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA. twang@wistar.org
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Ge
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lopez-Coral
authors.forename: Rikka
authors.initials: R
authors.lastname: Azuma
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.forename: Gao
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Rauscher
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: Russel E
authors.initials: RE
authors.lastname: Kaufman
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D016173:Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9