Chronic myelogenous leukemia cells convert to myofibroblasts in vitro: effect of vascular endothelial growth factor on development of the microenvironment.
To elucidate the biological characteristics of chronic myelogenous leukemia (CML) cells, we observed morphological and functional changes of CML cells during primary long-term culture, in which their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental CML cells including BCR-ABL fusion gene, and produced cytokines such as granulocyte colony-stimulating factor, interleukin-6, and vascular endothelial growth factor (VEGF)-A. When cultured on the CML-derived myofibroblasts, parental non-adherent CML cells significantly proliferated. When anti-VEGF-A-neutralizing antibody was added to the cultures, non-adherent CML cell proliferation was significantly inhibited. These observations indicate that CML cells can convert their morphology and function to adherent myofibroblasts, and produce a significant amount of cytokine to give a growth-promotion activity to CML cells.
Shirasaki
Ryosuke
R
Department of Hematology and Oncology, Teikyo University School of Medicine, Tokyo, Japan.
Tashiro
Haruko
H
Mizutani-Noguchi
Mitsuho
M
Kawasugi
Kazuo
K
Shirafuji
Naoki
N
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002469:Cell Separation; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000502:physiology; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor