B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules.
Initial work has shown that clonal B cells from B-chronic lymphocytic leukemia (B-CLL) are able to synthesize pro-angiogenic molecules. In this study, our goal was to study the spectrum of angiogenic factors and receptors expressed in the CLL B cell. We used ELISA assays to determine the levels of basic fibroblast growth factors (bFGF), vascular endothelial growth factor (VEGF), endostatin, interferon-alpha (IFN-alpha) and thrombospondin-1 (TSP-1) secreted into culture medium by purified CLL B cells. These data demonstrated that CLL B cells spontaneously secrete a variety of pro- and anti-angiogenic factors, including bFGF (23.9 pg/ml +/- 7.9; mean +/- s.e.m.), VEGF (12.5 pg/ml +/- 2.3) and TSP-1 (1.9 ng/ml +/- 0.3). Out of these three factors, CLL B cells consistently secreted bFGF and TSP-1, while VEGF was expressed in approximately two-thirds of CLL patients. Of interest, hypoxic conditions dramatically upregulated VEGF expression at both the mRNA and protein levels. We also employed ribonuclease protection assays to assay CLL B cell expression of a variety of other angiogenesis-related molecules. These analyses revealed that CLL B cells consistently express mRNA for VEGF receptor 1 (VEGFR1), thrombin receptor, endoglin, and angiopoietin. Further analysis of VEGFR expression by RT-PCR revealed that CLL B cells expressed both VEGFR1 mRNA and VEGFR2 mRNA. In summary, these data collectively indicate that CLL B cells express both pro- and anti-angiogenic molecules and several vascular factor receptors. Because of the co-expression of angiogenic molecules and receptors for some of these molecules, these data suggest that the biology of the leukemic cells may also be directly impacted by angiogenic factors as a result of autocrine pathways of stimulation.
Kay
N E
NE
Department of Medicine, Division of Hematology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Bone
N D
ND
Tschumper
R C
RC
Howell
K H
KH
Geyer
S M
SM
Dewald
G W
GW
Hanson
C A
CA
Jelinek
D F
DF
D020533:Angiogenesis Inhibitors / Q000096:biosynthesis*; D015703:Antigens, CD; D019898:Autocrine Communication; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D000071063:Endoglin; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism; D018095:Germ-Line Mutation; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D016898:Interferon-alpha / Q000032:analysis / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000032:analysis / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics; D018179:Receptors, Thrombin / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D019700:Thrombospondin 1 / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D043169:Endostatins; D016228:Endothelial Growth Factors; D006133:Growth Substances; D016898:Interferon-alpha; D008222:Lymphokines; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018179:Receptors, Thrombin; D019700:Thrombospondin 1; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1