title: Tumor galectin-1 mediates tumor growth and metastasis through regulation of T-cell apoptosis.
abstract: Galectin-1 (Gal-1), a carbohydrate-binding protein whose secretion is enhanced by hypoxia, promotes tumor aggressiveness by promoting angiogenesis and T-cell apoptosis. However, the importance of tumor versus host Gal-1 in tumor progression is undefined. Here we offer evidence that implicates tumor Gal-1 and its modulation of T-cell immunity in progression. Comparing Gal-1-deficient mice as hosts for Lewis lung carcinoma cells where Gal-1 levels were preserved or knocked down, we found that tumor Gal-1 was more critical than host Gal-1 in promoting tumor growth and spontaneous metastasis. Enhanced growth and metastasis associated with Gal-1 related to its immunomodulatory function, insofar as the benefits of Gal-1 expression to Lewis lung carcinoma growth were abolished in immunodeficient mice. In contrast, angiogenesis, as assessed by microvessel density count, was similar between tumors with divergent Gal-1 levels when examined at a comparable size. Our findings establish that tumor rather than host Gal-1 is responsible for mediating tumor progression through intratumoral immunomodulation, with broad implications in developing novel targeting strategies for Gal-1 in cancer.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Banh
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongbin
authors.initials: H
authors.lastname: Cao
authors.forename: Donna M
authors.initials: DM
authors.lastname: Bouley
authors.forename: Shirley
authors.initials: S
authors.lastname: Kwok
authors.forename: Christina
authors.initials: C
authors.lastname: Kong
authors.forename: Amato J
authors.initials: AJ
authors.lastname: Giaccia
authors.forename: Albert C
authors.initials: AC
authors.lastname: Koong
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D037483:Galectin 1