2.50
Hdl Handle:
http://hdl.handle.net/10541/70418
Title:
Eotaxin-2 and colorectal cancer: a potential target for immune therapy
Authors:
Cheadle, Eleanor J; Riyad, Kallingal; Subar, Daren; Rothwell, Dominic G; Ashton, Garry; Batha, Hayley; Sherlock, David J; Hawkins, Robert E; Gilham, David E
Abstract:
PURPOSE: 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.
Affiliation:
Cancer Research UK Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, University of Manchester, United Kingdom.
Citation:
Eotaxin-2 and colorectal cancer: a potential target for immune therapy. 2007, 13 (19):5719-28 Clin. Cancer Res.
Journal:
Clinical Cancer Research
Issue Date:
1-Oct-2007
URI:
http://hdl.handle.net/10541/70418
DOI:
10.1158/1078-0432.CCR-07-1145
PubMed ID:
17908961
Type:
Article
Language:
en
ISSN:
1078-0432
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorCheadle, Eleanor J-
dc.contributor.authorRiyad, Kallingal-
dc.contributor.authorSubar, Daren-
dc.contributor.authorRothwell, Dominic G-
dc.contributor.authorAshton, Garry-
dc.contributor.authorBatha, Hayley-
dc.contributor.authorSherlock, David J-
dc.contributor.authorHawkins, Robert E-
dc.contributor.authorGilham, David E-
dc.date.accessioned2009-06-12T15:32:34Z-
dc.date.available2009-06-12T15:32:34Z-
dc.date.issued2007-10-01-
dc.identifier.citationEotaxin-2 and colorectal cancer: a potential target for immune therapy. 2007, 13 (19):5719-28 Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid17908961-
dc.identifier.doi10.1158/1078-0432.CCR-07-1145-
dc.identifier.urihttp://hdl.handle.net/10541/70418-
dc.description.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.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectColorectal Canceren
dc.subjectLiver Canceren
dc.subjectCancer Metastasisen
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBiopsy-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Movement-
dc.subject.meshChemokine CCL2-
dc.subject.meshChemokine CCL24-
dc.subject.meshChemokines-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshImmune System-
dc.subject.meshImmunotherapy-
dc.subject.meshLiver Neoplasms-
dc.subject.meshNeoplasm Metastasis-
dc.titleEotaxin-2 and colorectal cancer: a potential target for immune therapyen
dc.typeArticleen
dc.contributor.departmentCancer Research UK Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, University of Manchester, United Kingdom.en
dc.identifier.journalClinical Cancer Researchen

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