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, Jin Lee Hee, Eric Sanchez, Steven J. Manyak, Dorina Gui, Dror Shalitin, Jonathan Said, Yunchao Chang, Thomas F. Deuel, Stavroula Baritaki, Benjamin Bonavida, James R. Berenson

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalBlood
Volume110
Issue number1
DOIs
StatePublished - Jul 1 2007

Fingerprint

Tumors
Multiple Myeloma
Growth
Neoplasms
Cells
Bone
Tissue
pleiotrophin
Cell Line
Severe Combined Immunodeficiency
Proteins
Antibodies
Gene expression
Bone Marrow Cells
Embryonic Development
Blood Proteins
Anti-Idiotypic Antibodies
Brain
Bone Marrow
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chen, H., Gordon, M. S., Campbell, R. A., Li, M., Wang, C. S., Hee, J. L., ... Berenson, J. R. (2007). Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth. Blood, 110(1), 287-295. https://doi.org/10.1182/blood-2006-08-042374

Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth. / Chen, Haiming; Gordon, Melinda S.; Campbell, Richard A.; Li, Mingjie; Wang, Cathy S.; Hee, Jin Lee; Sanchez, Eric; Manyak, Steven J.; Gui, Dorina; Shalitin, Dror; Said, Jonathan; Chang, Yunchao; Deuel, Thomas F.; Baritaki, Stavroula; Bonavida, Benjamin; Berenson, James R.

In: Blood, Vol. 110, No. 1, 01.07.2007, p. 287-295.

Research output: Contribution to journalArticle

Chen, H, Gordon, MS, Campbell, RA, Li, M, Wang, CS, Hee, JL, Sanchez, E, Manyak, SJ, Gui, D, Shalitin, D, Said, J, Chang, Y, Deuel, TF, Baritaki, S, Bonavida, B & Berenson, JR 2007, 'Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth', Blood, vol. 110, no. 1, pp. 287-295. https://doi.org/10.1182/blood-2006-08-042374
Chen H, Gordon MS, Campbell RA, Li M, Wang CS, Hee JL et al. Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth. Blood. 2007 Jul 1;110(1):287-295. https://doi.org/10.1182/blood-2006-08-042374
Chen, Haiming ; Gordon, Melinda S. ; Campbell, Richard A. ; Li, Mingjie ; Wang, Cathy S. ; Hee, Jin Lee ; Sanchez, Eric ; Manyak, Steven J. ; Gui, Dorina ; Shalitin, Dror ; Said, Jonathan ; Chang, Yunchao ; Deuel, Thomas F. ; Baritaki, Stavroula ; Bonavida, Benjamin ; Berenson, James R. / Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth. In: Blood. 2007 ; Vol. 110, No. 1. pp. 287-295.
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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.",
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AU - Gordon, Melinda S.

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AU - Wang, Cathy S.

AU - Hee, Jin Lee

AU - Sanchez, Eric

AU - Manyak, Steven J.

AU - Gui, Dorina

AU - Shalitin, Dror

AU - Said, Jonathan

AU - Chang, Yunchao

AU - Deuel, Thomas F.

AU - Baritaki, Stavroula

AU - Bonavida, Benjamin

AU - Berenson, James R.

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