Angiogenesis-, metastasis- and signaling pathway-related factor dynamics in human colon cancer cells following interaction with monocytes

Anticancer Res. 2013 Jul;33(7):2895-900.


Background: In tumors, monocytes differentiate into tumor-associated macrophages following interaction with cancer cells. We have previously reported that angiogenesis- and chemotaxis-related factors are associated with human monocyte differentiation following interaction with colon cancer cells. However, the exact nature of factors remains unknown. We investigated factors associated with differentiation of human colon cancer cells following interaction with monocytes.

Materials and methods: The human colon cancer cell line DLD-1 was co-cultured with the human monocyte cell line THP-1. mRNA expression was analyzed by quantitative real-time PCR.

Results: Expression of interleukin-1β, matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 increased in human colon cancer cells after co-culture with monocytes. Conversely, the expression of monocyte chemotactic protein-1, tumor necrosis factor-α, and signal transducer and activator of transcription-3 did not increase.

Conclusion: Differentiation of human colon cancer cells following interaction with monocytes may be associated with angiogenesis and metastasis but not chemotaxis and signaling pathways. Thus, angiogenesis- and metastasis-related factors associated with differentiation of human colon cancer cells may constitute important targets for colon cancer therapy.

Keywords: DLD-1; Monocyte; THP-1 cells; angiogenesis; co-culture; colon cancer cell; metastasis; signaling pathway.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Differentiation*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemotaxis
  • Coculture Techniques
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Biomarkers, Tumor
  • Chemokine CCL2
  • Interleukin-1beta
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1