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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
- Source :
- Blood, Blood, American Society of Hematology, 2004, 103 (5), pp.1829-37. ⟨10.1182/blood-2003-05-1510⟩
- Publication Year :
- 2004
- Publisher :
- HAL CCSD, 2004.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Database :
- OpenAIRE
- Journal :
- Blood, Blood, American Society of Hematology, 2004, 103 (5), pp.1829-37. ⟨10.1182/blood-2003-05-1510⟩
- Accession number :
- edsair.doi.dedup.....c3cbbdc4f75b07461b6b4edcc2565797