Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunothe
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BioMed Central
Open Access
Research
Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy John Stuart Gillis* Address: Science and Technology Studies, St. Thomas University, Fredericton, New Brunswick, Canada Email: John Stuart Gillis* - [email protected] * Corresponding author
Published: 04 July 2006 Journal of Translational Medicine 2006, 4:27
doi:10.1186/1479-5876-4-27
Received: 30 March 2006 Accepted: 04 July 2006
This article is available from: http://www.translational-medicine.com/content/4/1/27 © 2006 Gillis; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. Methods: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. Results: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. Conclusion: Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines.
Background In recent decades considerable progress has been made in developing methods which use the immune system to treat cancer. One particularly noteworthy series of events was the discovery of the first genes encoding human tumor antigens recognized by cytolytic T lymphocytes (CTLs) [1-3]. Since then, dozens of other antigen genes have been identified [4], many of which contain several short sequences of DNA, coding for peptides called "epitopes." When epitopes are bound by members of the
human leukocyte antigen (HLA) family, presented on the tumor cell surface, and recognized by CTLs; destruction of the tumor cell tends to occur. Scientists have become so adept at using such methods for reproducibly destroying tumor cells in the laboratory tha
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