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 Blood, 1 July 2007, Vol. 110, No. 1, pp. 287-295.
Prepublished online as a Blood First Edition Paper on March 16, 2007; DOI 10.1182/blood-2006-08-042374.

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NEOPLASIA

Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth

Haiming Chen1, Melinda S. Gordon1, Richard A. Campbell1, Mingjie Li1, Cathy S. Wang1, Hee Jin Lee1, Eric Sanchez1, Steven J. Manyak1, Dorina Gui2, Dror Shalitin1, Jonathan Said2, Yunchao Chang3, Thomas F. Deuel3, Stavroula Baritaki4, Benjamin Bonavida4, and James R. Berenson1

1 Institute for Myeloma & Bone Cancer Research, West Hollywood, CA; 2 Department of Pathology and Laboratory Medicine, Geffen School of Medicine at UCLA, University of California, Los Angeles; 3 Department of Molecular and Experimental Medicine and Cell Biology, The Scripps Research Institute, La Jolla, CA; 4 Department of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine at UCLA, University of California, Los Angeles

Pleiotrophin (PTN) is an important developmental cytokine that is highly expressed during embryogenesis but shows very limited expression in adult tissues, where it is largely restricted to the brain. High PTN serum levels are associated with a variety of solid tumors. We recently showed that patients with multiple myeloma (MM) also have elevated serum levels of this protein and the amount of PTN correlated with the patients' disease status and response to treatment. In this study, we demonstrate that MM cell lines and the malignant cells from MM patients' bone marrow produced PTN and secreted PTN protein into the supernatants during short-term culture. Moreover, Ptn gene expression correlated with the patients' disease status. Inhibition of PTN with a polyclonal anti-PTN antibody reduced growth and enhanced apoptosis of MM cell lines and freshly isolated bone marrow tumor cells from MM patients in vitro. Importantly, this antibody also markedly suppressed the growth of MM in vivo using a severe combined immunodeficiency (SCID)-hu murine model. This represents the first study showing the importance of PTN in the growth of any hematological disorder. Because the expression of this protein is very limited in normal adult tissues, PTN may represent a new target for the treatment of MM.


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