Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL-60 cells.
PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia (APL) involves differentiation therapy with retinoic acid (RA). However, the relapse rates are significant. In the present work we evaluated the effects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF-alpha, IL-8, and MMP-9 expression. This treatment induced higher levels of ICAM-1 endothelial cell expression, and increased cellular mobility. Inhibiting PDGFR enhanced RA-induced expression of integrin. Integrin ligand increased differentiation markers CD11b, inducible oxidative metabolism and PDGFR-beta phosphorylation. While the neutrophil-endothelial cell interactions are strengthened by the combined treatment, the endothelium-substratum interactions are weakened, a situation common in RAS.
Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, United States.
Gudrun
G
Reiterer
Rodica P
RP
Bunaciu
James L
JL
Smith
Andrew
A
Yen
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D018821:CD18 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D000075202:Contraindications; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013577:Syndrome; D014212:Tretinoin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020032:Tyrphostins / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018821:CD18 Antigens; D016209:Interleukin-8; D008024:Ligands; D016177:Macrophage-1 Antigen; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; D018799:Intercellular Adhesion Molecule-1; C106250:6,7-dimethoxy-3-phenylquinoxaline; D014212:Tretinoin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D020780:Matrix Metalloproteinase 9