title: Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth.
abstract: 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.
authors: Institute for Myeloma & Bone Cancer Research, West Hollywood, CA 90069, USA.
authors: Haiming
authors: H
authors: Chen
authors: Melinda S
authors: MS
authors: Gordon
authors: Richard A
authors: RA
authors: Campbell
authors: Mingjie
authors: M
authors: Li
authors: Cathy S
authors: CS
authors: Wang
authors: Hee Jin
authors: HJ
authors: Lee
authors: Eric
authors: E
authors: Sanchez
authors: Steven J
authors: SJ
authors: Manyak
authors: Dorina
authors: D
authors: Gui
authors: Dror
authors: D
authors: Shalitin
authors: Jonathan
authors: J
authors: Said
authors: Yunchao
authors: Y
authors: Chang
authors: Thomas F
authors: TF
authors: Deuel
authors: Stavroula
authors: S
authors: Baritaki
authors: Benjamin
authors: B
authors: Bonavida
authors: James R
authors: JR
authors: Berenson
mesh_terms: 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
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; C066845:pleiotrophin