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Blood, 15 October 2007, Vol. 110, No. 8, pp. 3028-3035. Prepublished online as a Blood First Edition Paper on July 20, 2007; DOI 10.1182/blood-2007-06-094417. This Article Full Text (PDF) All Versions of this Article: blood-2007-06-094417v1 110/8/3028    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, J. Articles by Yi, Q. Search for Related Content PubMed PubMed Citation Articles by Yang, J. Articles by Yi, Q. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 6, 2007 Accepted July 16, 2007 Anti-2-microglobulin monoclonal antibodies induce apoptosis in myeloma cells by recruiting MHC class I to and excluding growth and survival cytokine receptors from lipid rafts Jing Yang, Xiang Zhang, Ji Wang, Jianfei Qian, Liang Zhang, Michael Wang, Larry W. Kwak, and Qing Yi* Department of Lymphoma and Myeloma, Div of Cancer Medicine & the Center for Cancer Immunology Research, UT MD Anderson Cancer Center, Houston, TX * Corresponding author; email: qyi{at}mdanderson.org. We recently showed that monoclonal antibodies (mAbs) against 2M have a remarkably strong apoptotic effect on myeloma cells. The mAbs induced apoptosis by recruiting MHC class I to lipid rafts, activated JNK, and inhibited PI3K/Akt and ERK pathways. Growth and survival cytokines such as IL-6 and IGF-I, which could protect myeloma cells from dexamethasone-induced apoptosis, did not affect mAb-mediated cell death. This study was undertaken to elucidate the mechanisms underlying anti-2M mAb-induced PI3K/Akt and ERK inhibition and the inability of IL-6 and IGF-I to protect myeloma cells from mAb-induced apoptosis. We focused on lipid rafts and confirmed that these membrane microdomains are required for IL-6 and IGF-I signaling. By recruiting MHC class I into lipid rafts, anti-2M mAbs excluded IL-6 and IGF-I receptors and their substrates from the rafts. The mAbs were not only redistributed the receptors in cell membrane, but also abrogated IL-6- or IGF-I-mediated JAK/STAT3, PI3K/Akt, and Ras/Raf/ERK pathway signaling, which are otherwise constitutively activated in myeloma cells. Thus, this study further defines the tumoricidal mechanism of the mAbs and provides strong evidence to support the potential of these mAbs as therapeutic agents for myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Death by rafting Suzanne Lentzsch Blood 2007 110: 2791-2792. [Full Text] [PDF] This article has been cited by other articles: E. Spanoudakis, M. Hu, K. Naresh, E. Terpos, V. Melo, A. Reid, I. Kotsianidis, S. Abdalla, A. Rahemtulla, and A. Karadimitris Regulation of multiple myeloma survival and progression by CD1d Blood, March 12, 2009; 113(11): 2498 - 2507. [Abstract] [Full Text] [PDF] J. Yang, Y. Cao, S. Hong, H. Li, J. Qian, L. W. Kwak, and Q. Yi Human-Like Mouse Models for Testing the Efficacy and Safety of Anti-{beta}2-Microglobulin Monoclonal Antibodies to Treat Myeloma Clin. Cancer Res., February 1, 2009; 15(3): 951 - 959. [Abstract] [Full Text] [PDF]

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