Clinical & Experimental Metastasis

, Volume 24, Issue 2, pp 121–130 | Cite as

Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer

  • Charles Bailey
  • Rupert Negus
  • Alistair Morris
  • Paul Ziprin
  • Robert Goldin
  • Paola Allavena
  • David Peck
  • Ara Darzi
Research Paper


Chemokines promote tumour progression by enhancing proliferation and modifying the immune response. The purpose of this study was to test the hypothesis that CCL2 monocyte chemotactic protein-1 (MCP-1) contributes to the progression of colorectal cancer by influencing the number and distribution of tumour associated macrophages (TAMs). Chemokine expression was assessed in human colorectal adenocarcinomas by ribonuclease protection assay (RPA). Colonic adenocarcinoma cell lines were used to assess chemokine production by enzyme linked immunosorbant assay (ELISA), and Boyden microchemotaxis assays were performed to determine cell line supernatant monocyte chemotactic activity. CCL2 production was assessed in paraffin embedded tumour samples by immunohistochemistry. Finally, the number of macrophages and their distribution was determined in the same colorectal adenocarcinomas and compared with CCL2 expression and tumour stage. Results showed that CCL2 produced by cell lines induced monocyte chemoattraction, the expression of this chemokine in solid cancers increased with tumour stage (P < 0.05) and immunohistochemistry localized production to tumour cells. Analysis of the macrophage infiltrate showed that the accumulation was significantly greater in tumours than controls (P < 0.005) and within tumours it was greatest in necrotic regions (median 44,600 per mm3). Macrophage accumulation increased with tumour stage and correlated with CCL2 expression (rs = 0.8). CXCL8 interleukin 8 (IL-8), a potent angiogenic factor and growth factor, was expressed in all tumours and cell lines. It is concluded that CCL2 induces the accumulation of tumour promoting TAMs in human colorectal cancer and represents a therapeutic target to modify the macrophage response and direct immune mediated therapy.


Tumour associated macrophage (TAM) Leukocyte Cytokine Chemokine CCL2 (MCP-1) CXCL8 (IL-8) Colon cancer Rectal cancer 



Adenosine triphosphate




Enzyme linked immunosorbant assay


Fetal bovine serum


Glyceraldehyde-3-phosphate dehydrogenase


Interleukin 8


Interferon inducible protein 10




Monoclonal antibody


Monocyte chemotactic protein-1


Macrophage inflammatory protein 1 alpha


Macrophage inflammatory protein 1 beta


Matrix metalloproteinase-9


Phosphate buffered saline


Regulated on activation normal T-cell expressed and secreted


Ribonuclease protection assay


Standard error


Tumour associated macrophage


Tris-borate buffer


Tumour necrosis factor α




Vascular endothelial growth factor


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Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Charles Bailey
    • 1
    • 2
  • Rupert Negus
    • 3
  • Alistair Morris
    • 1
  • Paul Ziprin
    • 1
  • Robert Goldin
    • 4
  • Paola Allavena
    • 5
  • David Peck
    • 1
  • Ara Darzi
    • 1
  1. 1.Department of Surgical Oncology and TechnologySt Mary’s Hospital, Imperial College of Science, Technology, and MedicineLondonUK
  2. 2.Department of Colorectal SurgeryLevel 2, John Radcliffe HospitalOxfordUK
  3. 3.Department of GastroenterologySt Mary’s HospitalLondonUK
  4. 4.Department of PathologySt Mary’s Hospital, Imperial College of Science, Technology, and MedicineLondonUK
  5. 5.Istituto Clinico HumanitasRozzano, MilanItaly

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