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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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Submitted August 28, 2006
Accepted March 5, 2007

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

Haiming Chen, Melinda S Gordon, Richard A Campbell, Mingjie Li, Cathy S Wang, Hee Jin Lee, Eric Sanchez, Steven J Manyak, Dorina Gui, Dror Shalitin, Jonathan Said, Yunchao Chang, Thomas F Deuel, Stavroula Baritaki, Benjamin Bonavida, and James R Berenson*

Hematology/Oncology, Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, United States
Dept of Pathology and Laboratory Medicine, Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Dept of Molecular and Experimental Medicine and Cell Biology, The Scripps Research Institute, La Jolla, CA, United States
Dept of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine at UCLA, Los Angeles, CA, United States

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

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 multiple myeloma (MM) patients 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 demonstrated that MM cell lines and the malignant cells from MM patients' bone marrow (BM) 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 BM tumor cells from MM patients in vitro. Importantly, this antibody also markedly suppressed the growth of MM in vivo using a SCID-hu murine model. This represents the first study showing the importance of PTN in the growth of any hematological disorder. Since 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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