Identification of genes expressed in tumor-associated macrophages

Immunobiology. 2003;207(5):351-9. doi: 10.1078/0171-2985-00246.


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.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Cells, Cultured
  • Dipeptidases / genetics
  • Dipeptidases / metabolism
  • GPI-Linked Proteins
  • Gene Expression Regulation*
  • Humans
  • Interleukin-6 / metabolism
  • Macrophages / cytology
  • Macrophages / enzymology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Monocytes / cytology
  • Monocytes / immunology
  • Neoplasms / immunology*
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Antigens, CD
  • Antigens, Surface
  • CD180 protein, human
  • GPI-Linked Proteins
  • Interleukin-6
  • LY86 protein, human
  • RNA, Messenger
  • Dipeptidases
  • proline dipeptidase
  • carboxypeptidase M
  • Metalloendopeptidases