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Blood, 26 February 2009, Vol. 113, No. 9, pp. 1992-2002. Prepublished online as a Blood First Edition Paper on December 5, 2008; DOI 10.1182/blood-2008-02-133751. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-133751v1 113/9/1992    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, H. Articles by Berenson, J. R. Search for Related Content PubMed PubMed Citation Articles by Chen, H. Articles by Berenson, J. R. Related Collections Vascular Biology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis Haiming Chen1, Richard A. Campbell1, Yunchao Chang2, Mingjie Li1, Cathy S. Wang1, Jennifer Li1, Eric Sanchez1, Michael Share1, Jeffrey Steinberg1, Ariana Berenson1, Dror Shalitin1, Zhaohui Zeng3, Dorina Gui4, Pablo Perez-Pinera2, Ronald J. Berenson5, Jonathan Said4, Benjamin Bonavida6, Thomas F. Deuel2, and James R. Berenson1 1 Institute for Myeloma & Bone Cancer Research, West Hollywood, CA; 2 Department of Molecular and Experimental Medicine and Cell Biology, The Scripps Research Institute, La Jolla, CA; 3 Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA; 4 Department of Pathology, University of California at Los Angeles; 5 HemaQuest, Seattle, WA; 6 Department of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine, University of California at Los Angeles Enhanced angiogenesis is a hallmark of cancer. Pleiotrophin (PTN) is an angiogenic factor that is produced by many different human cancers and stimulates tumor blood vessel formation when it is expressed in malignant cancer cells. Recent studies show that monocytes may give rise to vascular endothelium. In these studies, we show that PTN combined with macrophage colony-stimulating factor (M-CSF) induces expression of vascular endothelial cell (VEC) genes and proteins in human monocyte cell lines and monocytes from human peripheral blood (PB). Monocytes induce VEC gene expression and develop tube-like structures when they are exposed to serum or cultured with bone marrow (BM) from patients with multiple myeloma (MM) that express PTN, effects specifically blocked with antiPTN antibodies. When coinjected with human MM cells into severe combined immunodeficient (SCID) mice, green fluorescent protein (GFP)–marked human monocytes were found incorporated into tumor blood vessels and expressed human VEC protein markers and genes that were blocked by anti-PTN antibody. Our results suggest that vasculogenesis in human MM may develop from tumoral production of PTN, which orchestrates the transdifferentiation of monocytes into VECs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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