title: VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine.
abstract: Evidence from human and animal studies support the hypothesis that psychological stress can be a co-factor for the initiation and progression of cancer. Recent work from our laboratory and others have shown that the catecholamine hormone, norepinephrine (NE), may influence tumor progression of some solid epithelial tumors including nasopharyngeal carcinoma (NPC) and ovarian cancer by modulating the expression of proangiogenic and pro-metastatic factors, such as vascular endothelial growth factor (VEGF). In this study, we determined whether NE can likewise modulate the expression of VEGF in a lymphoid tumor, multiple myeloma (MM), a cancer of plasma cells. Three MM-derived cell lines, NCI-H929, MM-M1, and FLAM-76, were studied. The presence of beta1- and beta2-adrenergic receptors (ARs) was assessed using Western blotting. Cells were treated with 0, 1, and 10 microM NE for 1, 3, 6, and 24h and the levels of VEGF in culture supernatants were measured by ELISA. Immunoblots of cell lysates revealed the presence of beta1- and beta2-ARs in all three MM-derived cell lines. However, these MM-derived cell lines exhibited varying degrees of NE-dependent regulation of VEGF expression with FLAM-76 (the only IL-6-dependent cell line among the three) exhibiting the most significant stimulation, followed by MM-M1 cells and then NCI-H929. The data suggest that the ability of NE to regulate the expression of VEGF is not limited to solid epithelial tumors and suggests a possible regulatory role of catecholamine stress hormones in MM progression.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Yang
authors.forename: Elise L
authors.initials: EL
authors.lastname: Donovan
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.forename: Ronald
authors.initials: R
authors.lastname: Glaser
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; D009638:Norepinephrine