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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.


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Submitted February 8, 2008
Accepted November 6, 2008

Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: A novel mechanism of tumor-induced vasculogenesis

Haiming Chen, Richard A Campbell, Yunchao Chang, Mingjie Li, Cathy S Wang, Jennifer Li, Eric Sanchez, Michael Share, Jeffrey Steinberg, Ariana Berenson, Dror Shalitin, Zhaohui Zeng, Dorina Gui, Pablo Perez-Pinera, Ronald J Berenson, Jonathan Said, Benjamin Bonavida, Thomas F Deuel, and James R Berenson*

Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, United States
Department of Molecular and Experimental Medicine and Cell Biology, The Scripps Research Institute, La Jolla, CA, United States
Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States
Department of Pathology, University of California at Los Angeles, Los Angeles, CA, United States
HemaQuest, Seattle, WA, United States
Department of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States

* Corresponding author; email: jberenson{at}imbcr.org.

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 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 anti-PTN antibodies. When co-injected with human MM cells into 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.


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