Identification of genes expressed in tumor-associated macrophages

Authors: Gottfried E.¹; Faust S.¹; Fritsche J.¹; Kunz-Schughart L.A.²; Andreesen R.¹; Miyake K.³; Kreutz M.¹

Source: Immunobiology, Volume 207, Number 5, September 2003 , pp. 351-359(9)

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Abstract:

Most malignant tumors contain so-called tumor-associated macrophages (TAM) as a major component of their leukocytic infiltrate. To investigate the impact of the tumor microenvironment on activation and differentiation of macrophages, we established a 3-dimensional model system by culturing human monocytes within multicellular tumor spheroids. After 7 days, monocyte-derived TAM were isolated and analyzed for phenotypic alterations as compared to macrophages cultured without tumor cell contact. We found the known macrophage differentiation marker Carboxypeptidase M to be suppressed while CD14, HLA-DR, and CD16 were up-regulated. Using Differential Display, we identified several genes that were differentially expressed between TAM and control macrophages. Prolidase, a peptidase known to influence the chemoattraction of neutrophils and macrophage activity, was down-regulated in TAM. In contrast, the Toll-like receptor family-related molecules MD-1 and RP105 were up-regulated by tumor cell contact, both at the RNA and protein level. From our data we conclude that TAM represent a distict macrophage population characterized by low expression of differentiation-associated macrophage antigens but also by a constitutive state of activation.

Document Type: Research article

DOI: http://dx.doi.org/10.1078/0171-2985-00246

Affiliations: 1: Dept. of Hematology and Oncology, University of Regensburg, Germany 2: Institute of Pathology, University of Regensburg, Germany 3: Dept. of Immunology, Saga Medical School, Japan

Publication date: 2003-09-01