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Eotaxin-2 and colorectal cancer: a potential target for immune therapy.

AbstractPURPOSE:
To study the production of chemokines by colorectal hepatic metastases.
EXPERIMENTAL DESIGN:
Biopsies of resected colorectal hepatic metastases and nonneoplastic adjacent liver tissue were screened for chemokines using protein arrays and results were confirmed by ELISA and immunohistochemistry.
RESULTS:
Two chemokines, eotaxin-2 and MCP-1, were found at elevated levels within the tumor biopsy compared with adjacent liver. The relative increase in expression from tumor was much higher for eotaxin-2 than MCP-1, with 10 of 25 donors having a >100-fold increase in expression compared with 0 of 24 donors for MCP-1. In a parallel analysis, eotaxin-2 was also found at elevated levels in the tumor region of primary colorectal cancer biopsies. Immunohistochemical staining indicated that carcinoembryonic antigen-positive tumor cells stained strongly for eotaxin-2, implicating these cells as the predominant source of the chemokine. In vitro studies confirmed that several colorectal tumor lines produce eotaxin-2 and that secretion of this chemokine could be depressed by IFN-gamma and enhanced by the Th2-type cytokines interleukin-4 and interleukin-13. Jurkat T cells were engineered to express the receptor for eotaxin-2 (CCR3). These cells effectively migrated in response to eotaxin-2 protein, suggesting that immune cells gene modified to express a chemokine receptor may have improved abilities to home to tumor.
CONCLUSIONS:
Taken together, these observations confirm eotaxin-2 as a chemokine strongly associated with primary and metastatic tumors of colorectal origin. Furthermore, the importance of this result may be a useful tool in the development of targeted therapeutic approaches to colorectal tumors.
AuthorsEleanor J Cheadle, Kallingal Riyad, Daren Subar, Dominic G Rothwell, Garry Ashton, Hayley Batha, David J Sherlock, Robert E Hawkins, David E Gilham
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 19 Pg. 5719-28 (Oct 01 2007) ISSN: 1078-0432 [Print] United States
PMID17908961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Chemokine CCL2
  • Chemokine CCL24
  • Chemokines
Topics
  • Antineoplastic Agents (therapeutic use)
  • Biopsy
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CCL2 (metabolism)
  • Chemokine CCL24 (physiology)
  • Chemokines (metabolism)
  • Colorectal Neoplasms (immunology, metabolism, therapy)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immune System
  • Immunotherapy (methods)
  • Liver Neoplasms (secondary)
  • Neoplasm Metastasis

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