Chronic myelogenous leukemia cells convert to myofibroblasts in vitro: effect of vascular endothelial growth factor on development of the microenvironment

Ryosuke Shirasaki; Haruko Tashiro; Mitsuho Mizutani-Noguchi; Kazuo Kawasugi; Naoki Shirafuji

doi:10.1016/j.leukres.2010.09.019

Chronic myelogenous leukemia cells convert to myofibroblasts in vitro: effect of vascular endothelial growth factor on development of the microenvironment

Leuk Res. 2011 May;35(5):663-9. doi: 10.1016/j.leukres.2010.09.019. Epub 2010 Oct 16.

Authors

Ryosuke Shirasaki¹, Haruko Tashiro, Mitsuho Mizutani-Noguchi, Kazuo Kawasugi, Naoki Shirafuji

Affiliation

¹ Department of Hematology and Oncology, Teikyo University School of Medicine, Tokyo, Japan.

PMID: 20952060
DOI: 10.1016/j.leukres.2010.09.019

Abstract

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.

MeSH terms

Adult
Cell Adhesion / drug effects
Cell Adhesion / genetics
Cell Adhesion / physiology
Cell Separation
Cell Transdifferentiation / drug effects
Cell Transdifferentiation / genetics
Cell Transdifferentiation / physiology
Cells, Cultured
Cytogenetic Analysis
Gene Expression Profiling
Gene Expression Regulation, Leukemic / drug effects
Gene Expression Regulation, Leukemic / physiology
Genes, abl / genetics
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
Myofibroblasts / metabolism
Myofibroblasts / pathology*
Myofibroblasts / physiology
Receptors, Vascular Endothelial Growth Factor / genetics
Receptors, Vascular Endothelial Growth Factor / metabolism
Tumor Microenvironment / drug effects*
Tumor Microenvironment / genetics
Tumor Microenvironment / physiology
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Vascular Endothelial Growth Factor A / pharmacology*

Substances

VEGFA protein, human
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor