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

Document Type

Article

Publication Date

7-1-2012

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. © 2012 John Wiley & Sons A/S.

Identifier

84862663385 (Scopus)

Publication Title

Pigment Cell and Melanoma Research

External Full Text Location

https://doi.org/10.1111/j.1755-148X.2012.01005.x

e-ISSN

1755148X

ISSN

17551471

PubMed ID

22498258

First Page

493

Last Page

505

Issue

4

Volume

25

Grant

P01CA025874

Fund Ref

National Cancer Institute

This document is currently not available here.

Share

COinS