title: The Beta Subunit of Hemoglobin (HBB2/HBB) Suppresses Neuroblastoma Growth and Metastasis.
abstract: Soluble pulmonary factors have been reported to be capable of inhibiting the viability of cancer cells that metastasize to the lung, but the molecular identity was obscure. Here we report the isolation and characterization of the beta subunit of hemoglobin as a lung-derived antimetastatic factor. Peptide mapping in the beta subunit of human hemoglobin (HBB) defined a short C-terminal region (termed Metox) as responsible for activity. In tissue culture, both HBB and murine HBB2 mediated growth arrest and apoptosis of lung-metastasizing neuroblastoma cells, along with a variety of other human cancer cell lines. Metox acted similarly and its administration in human tumor xenograft models limited the development of adrenal neuroblastoma tumors as well as spontaneous lung and bone marrow metastases. Expression studies in mice indicated that HBB2 is produced by alveolar epithelial and endothelial cells and is upregulated in mice bearing undetectable metastasis. Our work suggested a novel function for HBB as a theranostic molecule: an innate antimetastasis factor with potential utility as an anticancer drug and a biomarker signaling the presence of clinically undetectable metastasis. Cancer Res; 77(1); 14-26. ©2016 AACR.
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. isaacw@tauex.tau.ac.il Shellym3@post.tau.ac.il.|Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Shelly
authors: S
authors: Maman
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors: Orit
authors: O
authors: Sagi-Assif
authors: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Weirong
authors: W
authors: Yuan
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors: Ravit
authors: R
authors: Ginat
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors: Tsipi
authors: T
authors: Meshel
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors: Inna
authors: I
authors: Zubrilov
authors: Department of Clinical Microbiology and Immunology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Yona
authors: Y
authors: Keisari
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, P.R. China.
authors: Weiyue
authors: W
authors: Lu
authors: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Wuyuan
authors: W
authors: Lu
authors: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. isaacw@tauex.tau.ac.il Shellym3@post.tau.ac.il.|Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Isaac P
authors: IP
authors: Witz
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D006454:Hemoglobins / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D009447:Neuroblastoma / Q000556:secondary*
chemical_list: D006454:Hemoglobins