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Erschienen in: Angiogenesis 2/2012

01.06.2012 | Original Paper

VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients

verfasst von: Jon E. Peterson, David Zurakowski, Joseph E. Italiano Jr, Lea V. Michel, Susan Connors, Marsha Oenick, Robert J. D’Amato, Giannoula L. Klement, Judah Folkman

Erschienen in: Angiogenesis | Ausgabe 2/2012

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Abstract

Platelets sequester angiogenesis regulatory proteins which suggests an avenue for developing biomarkers to monitor disease. We describe a comparison of angiogenesis regulatory proteins found in platelets of colorectal cancer patients and normal controls. Platelet and plasma content of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1) and endostatin in 35 patients with colon cancer were compared with 84 age-matched healthy controls using ELISAs. We standardized the platelet preparation procedure, introduced process controls and normalized the respective protein levels to platelet numbers using an actin ELISA. Statistically significant differences were found in the median levels of VEGF, PF4 and PDGF in platelets of patients with cancer compared to healthy individuals. Platelet concentrations in cancer patients versus controls were: VEGF 1.3 versus 0.6 pg/106, PF4 18.5 versus 9.4 ng/106, and PDGF 34.1 versus 21.0 pg/106. Multivariable logistic regression analysis indicated that PDGF, PF4 and VEGF were independent predictors of colorectal carcinoma and as a set provided statistically significant discrimination (area under the curve = 0.893, P < .0001). No significant differences were detected for bFGF, endostatin, or TSP-1. Reference Change Value analysis determined that the differences seen were not clinically significant. Plasma levels yielded no correlations.
Literatur
2.
Zurück zum Zitat Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–287PubMedCrossRef Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–287PubMedCrossRef
3.
Zurück zum Zitat Fuhrmann-Benzakein E, Ma MN, Rubbia-Brandt L et al (2000) Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int J Cancer 85:40–45PubMedCrossRef Fuhrmann-Benzakein E, Ma MN, Rubbia-Brandt L et al (2000) Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int J Cancer 85:40–45PubMedCrossRef
5.
Zurück zum Zitat Peterson JE, Zurakowski D, Italiano JE Jr et al (2010) Normal ranges of angiogenesis regulatory proteins in human platelets. Amer. J. Hematology 85:487–493CrossRef Peterson JE, Zurakowski D, Italiano JE Jr et al (2010) Normal ranges of angiogenesis regulatory proteins in human platelets. Amer. J. Hematology 85:487–493CrossRef
6.
Zurück zum Zitat Klement GL, Kikuchi L, Kieran M (2004) Early tumor detection using platelet uptake of angiogenesis regulators. Blood 104 (abstr 839) Klement GL, Kikuchi L, Kieran M (2004) Early tumor detection using platelet uptake of angiogenesis regulators. Blood 104 (abstr 839)
7.
Zurück zum Zitat Klement GL, Yip T–T, Cassiola F et al (2009) Platelets actively sequester angiogenesis regulators. Blood 113:2835–2842PubMedCrossRef Klement GL, Yip T–T, Cassiola F et al (2009) Platelets actively sequester angiogenesis regulators. Blood 113:2835–2842PubMedCrossRef
8.
Zurück zum Zitat Saldago R, Benoy I, Bogers J et al (2001) Platelets and vascular endothelial growth factor (VEGF): a morphological and functional study. Angiogenesis 4:37–43CrossRef Saldago R, Benoy I, Bogers J et al (2001) Platelets and vascular endothelial growth factor (VEGF): a morphological and functional study. Angiogenesis 4:37–43CrossRef
9.
Zurück zum Zitat Gonzalez FJ, Rueda A, Sevilla I et al (2004) Shift in the balance between circulating thrombospondin-1 and vascular endothelial growth factor in cancer patients: Relationship to platelet a-granule content and primary activation. Int J Biol Markers 19:221–228PubMed Gonzalez FJ, Rueda A, Sevilla I et al (2004) Shift in the balance between circulating thrombospondin-1 and vascular endothelial growth factor in cancer patients: Relationship to platelet a-granule content and primary activation. Int J Biol Markers 19:221–228PubMed
10.
Zurück zum Zitat Hartwig JC (2008) The platelet cytoskeleton. In: Gresele P, Fuster V, López JA, Page CP, Vermylen J (eds) Platelets in hematologic and cardiovascular disorders. Cambridge University Press, New York, pp 75–97 Hartwig JC (2008) The platelet cytoskeleton. In: Gresele P, Fuster V, López JA, Page CP, Vermylen J (eds) Platelets in hematologic and cardiovascular disorders. Cambridge University Press, New York, pp 75–97
11.
Zurück zum Zitat Cervi D, Yip TT, Bhattacharya N et al (2008) Platelet-associated PF4 as a biomarker of early tumor growth. Blood 111:1201–1207PubMedCrossRef Cervi D, Yip TT, Bhattacharya N et al (2008) Platelet-associated PF4 as a biomarker of early tumor growth. Blood 111:1201–1207PubMedCrossRef
12.
Zurück zum Zitat Fraser CG (2001) Changes in serial results. In: Biological variation: from principals to practice. AACC Press, Washington, DC, pp 67–90 Fraser CG (2001) Changes in serial results. In: Biological variation: from principals to practice. AACC Press, Washington, DC, pp 67–90
13.
Zurück zum Zitat Grubbs F (1969) Procedures for detecting outlying observations in samples. Technometrics 11:1–21CrossRef Grubbs F (1969) Procedures for detecting outlying observations in samples. Technometrics 11:1–21CrossRef
14.
Zurück zum Zitat Altman DG (1991) Practical statistics for medical research. Chapman & Hall, Boca Raton, FL, pp 29–47 Altman DG (1991) Practical statistics for medical research. Chapman & Hall, Boca Raton, FL, pp 29–47
15.
Zurück zum Zitat Pepe MS (2003) The statistical evaluation of medical tests for classification and prediction. Oxford University Press, New York, pp 66–95 Pepe MS (2003) The statistical evaluation of medical tests for classification and prediction. Oxford University Press, New York, pp 66–95
16.
Zurück zum Zitat Katz MH (2006) Multivariable analysis: a practical guide for clinicians, 2nd edn. Cambridge University Press, New York, pp 96–136 Katz MH (2006) Multivariable analysis: a practical guide for clinicians, 2nd edn. Cambridge University Press, New York, pp 96–136
17.
Zurück zum Zitat Zaslavsky A, Baek K-H, Lynch RC et al (2010) Platelet-derived thrombospondin-1 (TSP-1) is a critical negative regulator and potential biomarker of angiogenesis. Blood 115:4605–4613PubMedCrossRef Zaslavsky A, Baek K-H, Lynch RC et al (2010) Platelet-derived thrombospondin-1 (TSP-1) is a critical negative regulator and potential biomarker of angiogenesis. Blood 115:4605–4613PubMedCrossRef
18.
Zurück zum Zitat Folkman J, Browder T, Palmblad J (2001) Angiogenesis research: guidelines for translation to clinical application. Thromb Haemost 86:23–33PubMed Folkman J, Browder T, Palmblad J (2001) Angiogenesis research: guidelines for translation to clinical application. Thromb Haemost 86:23–33PubMed
19.
Zurück zum Zitat George ML, Eccles SA, Tutton MG, Abulafi M, Swift RI (2000) Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: Clinical Evidence of Platelet Scavenging? Clin Cancer Res 6:3147–3152PubMed George ML, Eccles SA, Tutton MG, Abulafi M, Swift RI (2000) Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: Clinical Evidence of Platelet Scavenging? Clin Cancer Res 6:3147–3152PubMed
20.
Zurück zum Zitat Åkerblom B, Lindahl TL, Larsson A (2002) ADP activation induces bFGF binding to platelets in vitro. Upsala J Med Sci 107:165–171PubMedCrossRef Åkerblom B, Lindahl TL, Larsson A (2002) ADP activation induces bFGF binding to platelets in vitro. Upsala J Med Sci 107:165–171PubMedCrossRef
21.
Zurück zum Zitat Salgado R, Vermeulen PB, Benoy I et al (1999) Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients, Brit. J of Cancer 80:892–897CrossRef Salgado R, Vermeulen PB, Benoy I et al (1999) Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients, Brit. J of Cancer 80:892–897CrossRef
22.
Zurück zum Zitat Gasic GJ, Gasic TB, Stewart CC (1968) Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci USA 61:46–52PubMedCrossRef Gasic GJ, Gasic TB, Stewart CC (1968) Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci USA 61:46–52PubMedCrossRef
23.
Zurück zum Zitat Pedersen LM, Milman N (1996) Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respir J 9:1826–1830PubMedCrossRef Pedersen LM, Milman N (1996) Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respir J 9:1826–1830PubMedCrossRef
24.
Zurück zum Zitat Ikeda M, Furukawa H, Imamura H et al (2002) Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol 9:287–291PubMedCrossRef Ikeda M, Furukawa H, Imamura H et al (2002) Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol 9:287–291PubMedCrossRef
25.
Zurück zum Zitat Verheul HM, Hoekman K, Luykx-de Bakker S et al (1997) Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 3:2187–2190PubMed Verheul HM, Hoekman K, Luykx-de Bakker S et al (1997) Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 3:2187–2190PubMed
26.
Zurück zum Zitat Italiano JE Jr, Richardson JL, Patel-Hett S (2008) Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate alpha granules and differentially released. Blood 111:1227–1233PubMedCrossRef Italiano JE Jr, Richardson JL, Patel-Hett S (2008) Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate alpha granules and differentially released. Blood 111:1227–1233PubMedCrossRef
27.
Zurück zum Zitat Ma L, Perini R, McKnight W et al (2005) Proteinase activated receptors 1 and 4 counter-regulate endostatin and VEGF release from human platelets. Proc Natl Acad Sci USA 102:216–220PubMedCrossRef Ma L, Perini R, McKnight W et al (2005) Proteinase activated receptors 1 and 4 counter-regulate endostatin and VEGF release from human platelets. Proc Natl Acad Sci USA 102:216–220PubMedCrossRef
28.
Zurück zum Zitat Ellis LM, Takahashi Y, Liu W, Shaheen R (2000) Vascular endothelial growth factor in human colon cancer: Biology and therapeutic implications. Oncologist 5(suppl 1):11–15PubMedCrossRef Ellis LM, Takahashi Y, Liu W, Shaheen R (2000) Vascular endothelial growth factor in human colon cancer: Biology and therapeutic implications. Oncologist 5(suppl 1):11–15PubMedCrossRef
30.
Zurück zum Zitat Lindmark G, Sundberg C, Glimelius B (1993) Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer. Lab Invest 69(6):682–689PubMed Lindmark G, Sundberg C, Glimelius B (1993) Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer. Lab Invest 69(6):682–689PubMed
Metadaten
Titel
VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients
verfasst von
Jon E. Peterson
David Zurakowski
Joseph E. Italiano Jr
Lea V. Michel
Susan Connors
Marsha Oenick
Robert J. D’Amato
Giannoula L. Klement
Judah Folkman
Publikationsdatum
01.06.2012
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 2/2012
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-012-9259-z

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