Galectin-1 : a link between tumor hypoxia and tumor immune privilege
Le, Quynh T., Shi, Gongyi, Cao, Hongbin, Nelson, Daniel W., Wang, Yingyun, Chen, Eunice Y., Zhao, Shuchun, Kong, Christina, Richardson, Donna, O'Byrne, Kenneth J., Giaccia, Amato J., & Koong, Albert C. (2005) Galectin-1 : a link between tumor hypoxia and tumor immune privilege. Journal of Clinical Oncology, 23(35), pp. 8932-8941.
Purpose: To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression.
Methods: We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CDS (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes.
Results: SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O 2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CDS staining (P = .01). Expression of galectin-1 and CDS were significant predictors for overall survival on multivariate analysis.
Conclusion: Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege. © 2005 by American Society of Clinical Oncology.
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|Item Type:||Journal Article|
|Keywords:||carbonate dehydratase IX, CD3 antigen, galectin 1, adolescent, adult, aged, animal experiment, animal model, animal tissue, article, cancer cell culture, cancer growth, cancer staging, combined immunodeficiency, controlled study, enzyme linked immunosorbent assay, female, head and neck cancer, human, human cell, hypoxia, immunoblotting, major clinical study, male, mouse, nonhuman, priority journal, protein expression, real time polymerase chain reaction, squamous cell carcinoma, surface enhanced laser desorption ionization time of flight mass spectrometry, tandem mass spectrometry, treatment outcome, tumor immunity, xenograft, analysis of variance, animal, biosynthesis, cell hypoxia, disease course, enzyme immunoassay, head and neck tumor, immunology, mass spectrometry, metabolism, mouse mutant, pathology, polyacrylamide gel electrophoresis, polymerase chain reaction, prognosis, proportional hazards model, staining, survival, T lymphocyte, tumor cell line, Western blotting, Animals, Blotting, Western, Carcinoma, Squamous Cell, Cell Line, Tumor, Disease Progression, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Head and Neck Neoplasms, Humans, Immunoenzyme Techniques, Mice, Mice, SCID, Proportional Hazards Models, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Staining and Labeling, Survival Analysis, T-Lymphocytes|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2005 American Society of Clinical Oncology|
|Deposited On:||09 Dec 2013 03:33|
|Last Modified:||13 Jan 2014 06:37|
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