Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth.
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.
Chen
Haiming
H
Institute for Myeloma & Bone Cancer Research, West Hollywood, CA 90069, USA.
Gordon
Melinda S
MS
Campbell
Richard A
RA
Li
Mingjie
M
Wang
Cathy S
CS
Lee
Hee Jin
HJ
Sanchez
Eric
E
Manyak
Steven J
SJ
Gui
Dorina
D
Shalitin
Dror
D
Said
Jonathan
J
Chang
Yunchao
Y
Deuel
Thomas F
TF
Baritaki
Stavroula
S
Bonavida
Benjamin
B
Berenson
James R
JR
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D012720:Severity of Illness Index; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; C066845:pleiotrophin