Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth
| Autor: | Steven J. Manyak, Thomas F. Deuel, Benjamin Bonavida, Melinda S. Gordon, Dorina Gui, Haiming Chen, Yunchao Chang, Stavroula Baritaki, Richard A. Campbell, Hee Jin Lee, Dror Shalitin, Eric Sanchez, James R. Berenson, Cathy S. Wang, Jonathan W. Said, Mingjie Li |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_treatment
Immunology Apoptosis Mice SCID Biology Pleiotrophin Biochemistry Severity of Illness Index Antibodies Mice medicine Tumor Cells Cultured Animals Humans Tissue Distribution Multiple myeloma Cell Proliferation Severe combined immunodeficiency Cell Biology Hematology medicine.disease Molecular biology Neoplasm Proteins Gene Expression Regulation Neoplastic medicine.anatomical_structure Cytokine Cell culture Cancer research biology.protein Cytokines Bone marrow Antibody Carrier Proteins Multiple Myeloma |
| Zdroj: | Blood. 110(1) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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