Home LiteratureArticle Details
PMID: 9528841 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology.

British journal of cancer ·Vol. 77 ·No. 6 ·1998-03-00 ·Pages 956-64

Banks RE, Forbes MA, Kinsey SE, Stanley A, Ingham E, Walters C, Selby PJ

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including tumour vascularization. Our preliminary observations indicated higher VEGF concentrations in serum samples than in matched plasma samples. We have now demonstrated that this difference is due to the presence of VEGF within platelets and its release upon their activation during coagulation. In eight healthy volunteers, serum VEGF concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P < 0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9 to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other cell types within the bone marrow. From examination of the effects of blood sample processing on circulating VEGF concentrations, it is apparent that for accurate measurements, citrated plasma processed within 1 h of venepuncture should be used. Serum is completely unsuitable. The presence of VEGF within platelets has implications for processes involving platelet and endothelial cell interactions. e.g. wound healing, and in tumour metastasis, when platelets adhering to circulating tumour cells may release VEGF at points of adhesion to endothelium, leading to hyperpermeability and extravasation of cells.

MeSH Terms
Adult Biomarkers/blood Blood Platelets/cytology,physiology Blood Specimen Collection/methods Bone Marrow Cells/cytology Citrates Edetic Acid Endothelial Growth Factors/biosynthesis,blood Enzyme-Linked Immunosorbent Assay/methods Female Heparin Humans Immunohistochemistry Indicators and Reagents Lymphokines/biosynthesis,blood Male Megakaryocytes/cytology,physiology Middle Aged Reference Values Sensitivity and Specificity Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Biomarkers Citrates Endothelial Growth Factors Indicators and Reagents Lymphokines Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Heparin Edetic Acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Banks R E
ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds UK.
Forbes M A
Kinsey S E
Stanley A
Ingham E
Walters C
Selby P J
References (68)
68 references, click to expand
  1. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis.
    Cancer Res. 1995 Sep 15;55(18):4140-5 PMID: 7545086
  2. Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia.
    Obstet Gynecol. 1995 Nov;86(5):815-21 PMID: 7566855
  3. Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121.
    Cancer Res. 1995 Nov 15;55(22):5296-301 PMID: 7585591
  4. Sensitive chemiluminescence enzyme immunoassay for vascular endothelial growth factor/vascular permeability factor in human serum.
    Biosci Biotechnol Biochem. 1995 Oct;59(10):1958-9 PMID: 8534992
  5. 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.
    Cancer Res. 1995 Dec 1;55(23):5687-92 PMID: 7585655
  6. Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNF alpha and IL-6 levels and febrile transfusion reactions.
    Transfusion. 1993 Mar;33(3):195-9 PMID: 8438219
  7. Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.
    Oncogene. 1993 Apr;8(4):925-31 PMID: 7681160
  8. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis.
    Cell. 1993 Mar 26;72(6):835-46 PMID: 7681362
  9. Vascular endothelial growth factor is inactivated by binding to alpha 2-macroglobulin and the binding is inhibited by heparin.
    J Biol Chem. 1993 Apr 15;268(11):7685-91 PMID: 7681826
  10. Platelet alpha-granules.
    Blood Rev. 1993 Mar;7(1):52-62 PMID: 8467233
  11. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma.
    Int J Cancer. 1993 Sep 30;55(3):371-4 PMID: 7690738
  12. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas.
    Am J Pathol. 1993 Nov;143(5):1255-62 PMID: 8238242
  13. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705-9 PMID: 8248162
  14. Cytokine generation in stored platelet concentrates.
    Transfusion. 1994 Jan;34(1):20-5 PMID: 8273124
  15. Microvessel density and distribution in ductal carcinoma in situ of the breast.
    J Natl Cancer Inst. 1994 Apr 20;86(8):614-9 PMID: 7511693
  16. Effect of prestorage leukocyte removal on the cytokine levels in stored platelet concentrates.
    Vox Sang. 1994;66(1):14-7 PMID: 8146977
  17. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta.
    Growth Factors. 1993;9(4):259-68 PMID: 8148155
  18. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients.
    Biochim Biophys Acta. 1994 Mar 31;1221(2):211-4 PMID: 8148401
  19. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.
    Cancer Res. 1994 Aug 1;54(15):4233-7 PMID: 7518352
  20. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer.
    Jpn J Cancer Res. 1994 Oct;85(10):1045-9 PMID: 7525523
  21. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer.
    Hum Pathol. 1995 Jan;26(1):86-91 PMID: 7821921
  22. Effect of filtration of platelet concentrates on the accumulation of cytokines and platelet release factors during storage.
    Transfusion. 1995 Feb;35(2):117-24 PMID: 7825206
  23. Different angiogenic pathways characterize superficial and invasive bladder cancer.
    Cancer Res. 1995 Feb 1;55(3):510-3 PMID: 7530595
  24. Frequent overexpression of vascular endothelial growth factor gene in human renal cell carcinoma.
    Tohoku J Exp Med. 1994 Jul;173(3):355-60 PMID: 7846687
  25. Angiogenesis: an update.
    Histol Histopathol. 1994 Oct;9(4):807-43 PMID: 7534514
  26. Adverse reactions to platelet transfusions are reduced by use of platelet concentrates derived from buffy coat.
    Vox Sang. 1994;67(4):356-61 PMID: 7701806
  27. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis.
    J Clin Invest. 1995 Apr;95(4):1789-97 PMID: 7535799
  28. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma.
    J Natl Cancer Inst. 1995 Apr 5;87(7):506-16 PMID: 7707437
  29. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
    Am J Pathol. 1995 May;146(5):1029-39 PMID: 7538264
  30. The regulation of blood vessel growth by vascular endothelial growth factor.
    Ann N Y Acad Sci. 1995 Mar 27;752:246-56 PMID: 7538737
  31. Cytokines in platelet concentrates prepared from pooled buffy coats.
    Vox Sang. 1995;69(1):38-43 PMID: 7483490
  32. Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis.
    N Engl J Med. 1995 Dec 28;333(26):1757-63 PMID: 7491141
  33. Low cytokine contamination in buffy coat-derived platelet concentrates without filtration.
    Transfusion. 1995 Nov-Dec;35(11):917-20 PMID: 8604488
  34. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.
    Cancer Res. 1996 Jan 1;56(1):172-81 PMID: 8548760
  35. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
    Science. 1983 Feb 25;219(4587):983-5 PMID: 6823562
  36. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines.
    Cancer Res. 1986 Nov;46(11):5629-32 PMID: 3756910
  37. Activated platelets express IL-1 activity.
    J Immunol. 1989 Dec 15;143(12):4015-8 PMID: 2592766
  38. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family.
    Oncogene. 1990 Apr;5(4):519-24 PMID: 2158038
  39. Vascular endothelial growth factor, a potent and selective angiogenic agent.
    J Biol Chem. 1996 Jan 12;271(2):603-6 PMID: 8557658
  40. Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence.
    Cancer Res. 1996 Jan 15;56(2):393-401 PMID: 8542597
  41. Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor.
    Int J Hematol. 1995 Dec;62(4):203-15 PMID: 8589366
  42. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome.
    Lancet. 1996 Mar 9;347(9002):702 PMID: 8596427
  43. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.
    EMBO J. 1996 Jan 15;15(2):290-98 PMID: 8617204
  44. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele.
    Nature. 1996 Apr 4;380(6573):435-9 PMID: 8602241
  45. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.
    Nature. 1996 Apr 4;380(6573):439-42 PMID: 8602242
  46. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.
    Blood. 1996 Apr 15;87(8):3336-43 PMID: 8605350
  47. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma.
    Cancer. 1996 Mar 1;77(5):858-63 PMID: 8608475
  48. Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma.
    Br J Cancer. 1996 Apr;73(7):931-4 PMID: 8611409
  49. Vascular endothelial growth factor B, a novel growth factor for endothelial cells.
    Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2576-81 PMID: 8637916
  50. Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients.
    Cancer Res. 1996 May 1;56(9):2185-90 PMID: 8616870
  51. Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.
    Surgery. 1996 Mar;119(3):333-9 PMID: 8619189
  52. Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively.
    Circulation. 1996 Mar 15;93(6):1079-82 PMID: 8653826
  53. Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms.
    Lab Invest. 1996 Jun;74(6):1105-15 PMID: 8667614
  54. Cloning and characterization of a novel human gene related to vascular endothelial growth factor.
    Genome Res. 1996 Feb;6(2):124-31 PMID: 8919691
  55. Serum and urinary vascular endothelial growth factor levels in non-small cell lung cancer patients.
    Eur J Cancer. 1996 Dec;32A(13):2368-9 PMID: 9038626
  56. Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre-eclampsia.
    Br J Obstet Gynaecol. 1997 Feb;104(2):223-8 PMID: 9070144
  57. Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients.
    Br J Cancer. 1997;76(2):238-43 PMID: 9231925
  58. Tumor interactions with the vasculature: angiogenesis and tumor metastasis.
    Biochim Biophys Acta. 1990 Jun 1;1032(1):89-118 PMID: 1694687
  59. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing.
    J Biol Chem. 1991 Jun 25;266(18):11947-54 PMID: 1711045
  60. Identification of a new endothelial cell growth factor receptor tyrosine kinase.
    Oncogene. 1991 Sep;6(9):1677-83 PMID: 1656371
  61. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9026-30 PMID: 1717995
  62. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9267-71 PMID: 1924389
  63. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA.
    Mol Endocrinol. 1991 Dec;5(12):1806-14 PMID: 1791831
  64. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.
    Science. 1992 Feb 21;255(5047):989-91 PMID: 1312256
  65. Angiogenesis.
    J Biol Chem. 1992 Jun 5;267(16):10931-4 PMID: 1375931
  66. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.
    J Biol Chem. 1992 Dec 25;267(36):26031-7 PMID: 1464614
  67. Increased intraplatelet and urinary transforming growth factor-beta in patients with multiple myeloma.
    Acta Haematol. 1995;94(1):1-6 PMID: 7653206
  68. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
    Cancer Res. 1995 Sep 15;55(18):3964-8 PMID: 7664263
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/bjc.1998.158
Published
1998-03-00
Pages
956-64
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2150108
Subset
IM
Corrections
CommentIn
PMID: 9888483
External Links
PubMed source DOI: 10.1038/bjc.1998.158 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2