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Expression of the Vascular Endothelial Growth Factor (VEGF) Receptor Gene, KDR, in Hematopoietic Cells and Inhibitory Effect of VEGF on Apoptotic Cell Death Caused by Ionizing Radiation

Departments of Environment and Mutation [O. K., K. K., A. K., Y. S.] and Radiation Biology [H. T.], Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima-shi 734, Japan

Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we demonstrated the expression of the KDR gene transcript, which encodes a cell surface receptor for VEGF, in normal human hematopoietic stem cells, megakaryocytes, and platelets as well as in human leukemia cell lines, HEL and CMK86. Moreover, we showed the expression of VEGF gene transcript in these normal fresh cells and cell lines. To elucidate biological functions of VEGF on hematopoiesis, we determined whether this growth factor has mitogenic activity to hematopoietic cells or the ability to suppress apoptotic cell death. The liquid culture and colonyformation assay revealed that VEGF suppressed apoptotic cell death of both CMK86 cells and normal hematopoietic stem cells caused by gammaray irradiation, although mitogenic activity of VEGF was not detected. The ability of VEGF to suppress apoptotic cell death was independent of the change of cell cycle distribution. These data suggest that VEGF may play an important role in survival or maintenance of hematopoietic stem cells due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation and that VEGF may give leukemia cells some abilities of resistance against radiotherapy in an autocrine or paracrine manner.

¹ To whom requests for reprints should be addressed. Phone: 81-82-257-5818; Fax: 81-82-256-7104.

Received 7/ 7/95. Accepted 9/29/95.

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