Originally published as JCO Early Release 10.1200/JCO.2005.02.0206 on October 11 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le, Q.-T. Articles by Koong, A. C. Search for Related Content PubMed PubMed Citation Articles by Le, Q.-T. Articles by Koong, A. C. Social Bookmarking                            What's this?

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

Quynh-Thu Le, Gongyi Shi, Hongbin Cao, Daniel W. Nelson, Yingyun Wang, Eunice Y. Chen, Shuchun Zhao, Christina Kong, Donna Richardson, Ken J. O'Byrne, Amato J. Giaccia, Albert C. Koong

From the Departments of Radiation Oncology, Otolaryngology, and Pathology, Stanford University, Stanford, CA; and the Departments of Oncology, Pathology, and Epidemiology, University Hospitals of Leicester National Health Service Trust, United Kingdom

Address reprint requests to Quynh-Thu Le, MD, Department of Radiation Oncology, Stanford University Medical Center, 875 Blake Wilbur Drive, Rm # CCG-228, Stanford, CA 94305-5847; e-mail: qle{at}stanford.edu.

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 CD3 (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% 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.

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.

Supported by US Public Health Service Grant No. CA-67166 (Q.-T.L. and A.J.G.), the Damon Runyon–Lilly Clinical Investigator Award (A.C.K.), the Stanford Cancer Council Grant (C.K.), and the Stanford Office of Technology and Development Award (G.S.).

Presented in part at the 2004 Annual Meeting of the American Society of Therapeutic Radiology and Oncology, Atlanta, GA, October 3-7, 2004.

Q.-T.L. and G.S. contributed equally to this work

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Yuditskaya, A. Tumblin, G. T. Hoehn, G. Wang, S. K. Drake, X. Xu, S. Ying, A. H. Chi, A. T. Remaley, R.-F. Shen, et al. Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease Blood, January 29, 2009; 113(5): 1122 - 1128. [Abstract] [Full Text] [PDF]

				S. J. Rodig, J. Ouyang, P. Juszczynski, T. Currie, K. Law, D. S. Neuberg, G. A. Rabinovich, M. A. Shipp, and J. L. Kutok AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features Clin. Cancer Res., June 1, 2008; 14(11): 3338 - 3344. [Abstract] [Full Text] [PDF]

				V. L. J. L. Thijssen, F. Poirier, L. G. Baum, and A. W. Griffioen Galectins in the tumor endothelium: opportunities for combined cancer therapy Blood, October 15, 2007; 110(8): 2819 - 2827. [Abstract] [Full Text] [PDF]

				P. Juszczynski, J. Ouyang, S. Monti, S. J. Rodig, K. Takeyama, J. Abramson, W. Chen, J. L. Kutok, G. A. Rabinovich, and M. A. Shipp The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma PNAS, August 7, 2007; 104(32): 13134 - 13139. [Abstract] [Full Text] [PDF]

				H. F. Valenzuela, K. E. Pace, P. V. Cabrera, R. White, K. Porvari, H. Kaija, P. Vihko, and L. G. Baum O-Glycosylation Regulates LNCaP Prostate Cancer Cell Susceptibility to Apoptosis Induced by Galectin-1 Cancer Res., July 1, 2007; 67(13): 6155 - 6162. [Abstract] [Full Text] [PDF]

				D. Case, D. Irwin, C. Ivester, J. Harral, K. Morris, M. Imamura, M. Roedersheimer, A. Patterson, M. Carr, M. Hagen, et al. Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L154 - L164. [Abstract] [Full Text] [PDF]

				I. Camby, M. Le Mercier, F. Lefranc, and R. Kiss Galectin-1: a small protein with major functions Glycobiology, November 1, 2006; 16(11): 137R - 157R. [Abstract] [Full Text] [PDF]

				C. H. Chung, J. S. Parker, K. Ely, J. Carter, Y. Yi, B. A. Murphy, K. K. Ang, A. K. El-Naggar, A. M. Zanation, A. J. Cmelak, et al. Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-{kappa}B Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma Cancer Res., August 15, 2006; 66(16): 8210 - 8218. [Abstract] [Full Text] [PDF]