B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules

• Published in: Leukemia Vol. 16; no. 5; pp. 911 - 919
• Main Authors: KAY, N. E, BONE, N. D, TSCHUMPER, R. C, HOWELL, K. H, GEYER, S. M, DEWALD, G. W, HANSON, C. A, JELINEK, D. F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.05.2002; Nature Publishing Group
• Subjects: Angiogenesis; Angiogenesis Inhibitors - biosynthesis; Angiopoietin; Antiangiogenics; Antigens, CD; Assaying; Autocrine Communication; Autocrine signalling; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; B-Lymphocytes - secretion; Biological and medical sciences; Cancer cells; Cell culture; Chemical synthesis; Chronic lymphocytic leukemia; Clone Cells - metabolism; Clone Cells - pathology; Clone Cells - secretion; Cohort Studies; Collagen - analysis; Collagen - secretion; Development and progression; Endoglin; Endostatin; Endostatins; Endothelial Growth Factors - analysis; Endothelial Growth Factors - secretion; Enzyme-linked immunosorbent assay; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - analysis; Fibroblast Growth Factor 2 - secretion; Gene expression; Germ-Line Mutation; Growth factors; Growth Substances - biosynthesis; Hematologic and hematopoietic diseases; Humans; Hypoxia; Interferon; Interferon-alpha - analysis; Interferon-alpha - secretion; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Lymphocytes B; Lymphokines - analysis; Lymphokines - secretion; Medical sciences; mRNA; Neovascularization; Peptide Fragments - analysis; Peptide Fragments - secretion; Physiological aspects; Polymerase chain reaction; Proto-Oncogene Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Receptors; Receptors, Cell Surface; Receptors, Growth Factor - biosynthesis; Receptors, Growth Factor - genetics; Receptors, Thrombin - genetics; Receptors, Vascular Endothelial Growth Factor; Ribonuclease; RNA, Messenger - metabolism; Thrombin; Thrombospondin; Thrombospondin 1 - analysis; Thrombospondin 1 - secretion; Tumor Cells, Cultured; Vascular Cell Adhesion Molecule-1 - genetics; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular endothelial growth factor receptors; Vascular Endothelial Growth Factors; α-Interferon; United States; Human; Prognosis; Angiogenic factor; Pathophysiology; Malignant hemopathy; B-Lymphocyte; Angiogenesis; Chronic; Chronic lymphocytic leukemia; Vascular endothelium growth factor; Lymphoproliferative syndrome; Inhibitor; Biological receptor; Thrombospondin
• DOI: 10.1038/sj.leu.2402467
• ISSN: 0887-6924

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.