title: Eotaxin-2 and colorectal cancer: a potential target for immune therapy.
abstract: OBJECTIVE
  To study the production of chemokines by colorectal hepatic metastases.
  
  
  METHODS
  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.
authors.affiliation: Cancer Research UK Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, University of Manchester, United Kingdom.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Cheadle
authors.forename: Kallingal
authors.initials: K
authors.lastname: Riyad
authors.forename: Daren
authors.initials: D
authors.lastname: Subar
authors.forename: Dominic G
authors.initials: DG
authors.lastname: Rothwell
authors.forename: Garry
authors.initials: G
authors.lastname: Ashton
authors.forename: Hayley
authors.initials: H
authors.lastname: Batha
authors.forename: David J
authors.initials: DJ
authors.lastname: Sherlock
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hawkins
authors.forename: David E
authors.initials: DE
authors.lastname: Gilham
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D045744:Cell Line, Tumor; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D054423:Chemokine CCL24 / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000556:secondary*; D009362:Neoplasm Metastasis
chemical_list: D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D054423:Chemokine CCL24; D018925:Chemokines