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

Neil Elliot Kay, N. D. Bone, R. C. Tschumper, K. H. Howell, S. M. Geyer, G. W. Dewald, C. A. Hanson, Diane F Jelinek

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

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-α (IFN-α) 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.

Original languageEnglish (US)
Pages (from-to)911-919
Number of pages9
JournalLeukemia
Volume16
Issue number5
DOIs
StatePublished - 2002

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Keywords

  • B-CLL
  • TSP-1
  • Vascular factors
  • VEGF

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Kay, N. E., Bone, N. D., Tschumper, R. C., Howell, K. H., Geyer, S. M., Dewald, G. W., Hanson, C. A., & Jelinek, D. F. (2002). B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules. Leukemia, 16(5), 911-919. https://doi.org/10.1038/sj.leu.2402467