An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis
| Autor: | Michel Jourdan, Catherine Hertogh, Eric Jourdan, Karène Mahtouk, Jean-François Rossi, John De Vos, Geneviève Fiol, Bernard Klein |
|---|---|
| Přispěvatelé: | Frei, Monique, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Receptor
ErbB-4 Cellular differentiation medicine.medical_treatment Lipopolysaccharide Receptors Apoptosis Cell Separation Biochemistry Dexamethasone Monocytes Phosphatidylinositol 3-Kinases Epidermal growth factor immune system diseases hemic and lymphatic diseases Plasma cell differentiation Enzyme Inhibitors Multiple myeloma Cells Cultured Reverse Transcriptase Polymerase Chain Reaction MESH: Antigens CD14 MESH: Bone Marrow Cells Cell Differentiation Drug Synergism Hematology MESH: Antineoplastic Agents Hormonal ErbB Receptors medicine.anatomical_structure MESH: Dexamethasone Intercellular Signaling Peptides and Proteins MESH: Cell Division Electrophoresis Polyacrylamide Gel Multiple Myeloma hormones hormone substitutes and hormone antagonists Cell Division Heparin-binding EGF-like Growth Factor MESH: Cells Cultured MESH: Cell Differentiation Stromal cell MESH: Cell Line Tumor Antineoplastic Agents Hormonal Immunology Blotting Western Bone Marrow Cells Biology Sensitivity and Specificity MESH: Cell Separation Article MESH: Cell Adhesion Growth factor receptor Cell Line Tumor medicine Cell Adhesion [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans MESH: Blotting Western [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Epidermal Growth Factor Interleukin-6 Growth factor MESH: Apoptosis Cell Biology MESH: 1-Phosphatidylinositol 3-Kinase medicine.disease Hematopoietic Stem Cells Cancer research Leukocytes Mononuclear Bone marrow MESH: Drug |
| Zdroj: | Blood Blood, American Society of Hematology, 2004, 103 (5), pp.1829-37. ⟨10.1182/blood-2003-05-1510⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2003-05-1510 |
| Popis: | We previously found that some myeloma cell lines express the heparin-binding epidermal growth factor–like growth factor (HB-EGF) gene. As the proteoglycan syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell differentiation and a marker of myeloma cells, we studied the role of HB-EGF on myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear cells in 8 of 8 patients with myeloma, particularly by monocytes and stromal cells, but not by purified primary myeloma cells. Six of 9 myeloma cell lines and 9 of 9 purified primary myeloma cells expressed ErbB1 or ErbB4 genes coding for HB-EGF receptor. In the presence of a low interleukin-6 (IL-6) concentration, HB-EGF stimulated the proliferation of the 6 ErbB1+ or ErbB4+ cell lines, through the phosphatidylinositol 3-kinase/AKT (PI-3K/AKT) pathway. A pan-ErbB inhibitor blocked the myeloma cell growth factor activity and the signaling induced by HB-EGF. This inhibitor induced apoptosis of patients'myeloma cells cultured with their tumor environment. It also increased patients' myeloma cell apoptosis induced by an anti–IL-6 antibody or dexamethasone. The ErbB inhibitor had no effect on the interaction between multiple myeloma cells and stromal cells. It was not toxic for nonmyeloma cells present in patients' bone marrow cultures or for the growth of hematopoietic progenitors. Altogether, these data identify ErbB receptors as putative therapeutic targets in multiple myeloma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|