Title | The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | St Hill CA, Farooqui M, Mitcheltree G, H Gulbahce E, Jessurun J, Cao Q, Walcheck B |
Journal | BMC Cancer |
Volume | 9 |
Pagination | 79 |
Date Published | 2009 Mar 06 |
ISSN | 1471-2407 |
Keywords | Adenocarcinoma, Antigens, Neoplasm, Biomarkers, Tumor, Carbohydrate Metabolism, Colon, Colorectal Neoplasms, E-Selectin, Humans, Immunohistochemistry, Liver, Liver Neoplasms, N-Acetylglucosaminyltransferases, Neoplasm Metastasis, Neoplasm Staging, Polysaccharides, Prognosis, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger |
Abstract | BACKGROUND: The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLex) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLex (C2-O-sLex). Our goal was to determine the expression profiles of C2-O-sLex in the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLex present in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLex was present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR). RESULTS: We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components.Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT-PCR. Significantly, we observed a greater than 15-fold increase in C2GnT1 mRNA levels in colorectal adenocarcinomas compared to normal colorectal tissues. CONCLUSION: C2-O-sLex, detected by the CHO-131 mAb, is a tumor associated antigen whose expression is highly upregulated in colorectal adenocarcinomas and metastatic liver tumors compared to normal tissues. C2-O-sLex is a potentially useful early predictor of metastasis. |
DOI | 10.1186/1471-2407-9-79 |
Alternate Journal | BMC Cancer |
PubMed ID | 19267921 |
Grant List | 5KO8CA111829-03 / CA / NCI NIH HHS / United States |
Related Faculty:
Jose Jessurun, M.D.