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Role of vascular endothelial growth factor (VEGF) and placenta‐derived growth factor (PlGF) in regulating human haemopoietic cell growth
Author(s) -
Ratajczak Mariusz Z.,
Ratajczak Janina,
Machalinski Bogdan,
Majka Marcin,
Marlicz Wojtek,
Carter Anna,
Pietrzkowski Zbigniew,
Gswirtz Alan M.
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.01076.x
Subject(s) - biology , haematopoiesis , vascular endothelial growth factor , placental growth factor , progenitor cell , growth factor , medicine , stem cell , stem cell factor , endocrinology , kinase insert domain receptor , cord blood , myeloid , cd34 , vascular endothelial growth factor a , receptor , immunology , cancer research , microbiology and biotechnology , vegf receptors , biochemistry
Vascular endothelial growth factor (VEGF) and placental derived growth factor (PlGF) stimulate cell proliferation and differentiation by binding to their specific receptors, Flk‐1/KDR and Flt‐1 respectively. Flk‐1/KDR‐deficient murine embryos manifest failure of blood‐island formation and vasculogenesis. The aim of this study was to directly evaluate the importance of VEGF, PlGF/Flt‐1 and Flk‐1/KDR receptor ligand interactions in regulating normal and malignant human haemopoiesis. Addition of VEGF and PlGF failed to enhance survival or cloning efficiency of human haemopoietic progenitors isolated from adult bone marrows, fetal livers or cord blood samples. This finding may be explained by the apparent absence of mRNA encoding Flt‐1 and Flk‐1/KDR receptors on stem cell rich CD34 + c‐kit‐R + Rh123 low cells. Further studies revealed that Flt‐1 R mRNA, but not Flk‐1/KDR mRNA was first detectable in the more mature cells isolated from haemopoietic colonies. Accordingly, VEGF receptors are either absent, or expressed at very low level, on human haemopoietic stem/progenitor cells. Of interest, normal and malignant human haemopoietic cells appeared to secrete VEGF protein. However, in contrast to normal haemopoietic progenitors, VEGF co‐stimulated HEL cell proliferation as well as CFU‐GM colony formation from ∼15% of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) patients studied. Therefore, although VEGF appeared to have minimal effects on normal haemopoietic cell growth it would appear to drive malignant haemopoietic cell proliferation to some degree. Of more importance, however, we speculate that VEGF may play an very important role in leukaemogenesis by stimulating growth of vascular endothelium, thereby providing a sufficient blood supply to feed the growing haematological tumour.