TY - JOUR
T1 - Melanoma-derived conditioned media efficiently induce the differentiation of monocytes to macrophages that display a highly invasive gene signature
AU - Wang, Tao
AU - Ge, Yingbin
AU - Xiao, Min
AU - Lopez-Coral, Alfonso
AU - Azuma, Rikka
AU - Somasundaram, Rajasekharan
AU - Zhang, Gao
AU - Wei, Zhi
AU - Xu, Xiaowei
AU - Rauscher, Frank J.
AU - Herlyn, Meenhard
AU - Kaufman, Russel E.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Glycoprotein non-metastatic melanoma protein B
KW - Invasion
KW - Macrophages
KW - Melanoma
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84862663385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862663385&partnerID=8YFLogxK
U2 - 10.1111/j.1755-148X.2012.01005.x
DO - 10.1111/j.1755-148X.2012.01005.x
M3 - Article
C2 - 22498258
AN - SCOPUS:84862663385
SN - 1755-1471
VL - 25
SP - 493
EP - 505
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
IS - 4
ER -