Galectin-1: A Link Between Tumor Hypoxia and Tumor Immune Privilege

• Published in: Journal of clinical oncology Vol. 23; no. 35; pp. 8932 - 8941
• Main Authors: Le, Quynh-Thu, Shi, Gongyi, Cao, Hongbin, Nelson, Daniel W, Wang, Yingyun, Chen, Eunice Y, Zhao, Shuchun, Kong, Christina, Richardson, Donna, O'Byrne, Ken J, Giaccia, Amato J, Koong, Albert C
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 10.12.2005; Lippincott Williams & Wilkins
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Blotting, Western; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Hypoxia; Cell Line, Tumor; Disease Progression; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Galectin 1 - biosynthesis; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Immunoenzyme Techniques; Medical sciences; Mice; Mice, SCID; Polymerase Chain Reaction; Prognosis; Proportional Hazards Models; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining and Labeling; Survival Analysis; T-Lymphocytes - immunology; Tumors; Hypoxia; Tumor; Oxygen; Cancerology; Galectin 1
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.02.0206

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. 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 CD3 (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. 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% O2 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 CD3 staining (P = .01). Expression of galectin-1 and CD3 were significant predictors for overall survival on multivariate analysis. 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.