VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients (original) (raw)

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.

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Abbreviations

VEGF:

Vascular endothelial growth factor

bFGF:

Basic fibroblast growth factor

PDGF:

Platelet derived growth factor

PF4:

Platelet factor 4

TSP-1:

Thrombospondin-1

PRP:

Platelet rich plasma

PPP:

Platelet poor plasma

CBC:

Complete blood count

CRC:

Colorectal cancer

ELISA:

Enzyme linked immune sorbent assay

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Acknowledgments

This paper is dedicated to Judah Folkman, MD. We thank Dr. Marsha Moses of Children’s Hospital Boston for a helpful review of this manuscript. We thank Betsy Valles of Massachusetts General Hospital and Sean Downing of Children’s Hospital Boston and for their work in collecting and archiving cancer patient samples. We thank Dennis Robords of Ortho Clinical Diagnostics, Abdo Abou-Slaybi and Marlieke de Bruin of Children’s Hospital Boston for technical assistance. We thank Sean Downing of Children’s Hospital Boston and Lucius (Tad) Fox and John Backus of Ortho Clinical Diagnostics for discussions. We also thank John Backus for providing colonoscopy samples from Mayo Clinic. Ortho Clinical Diagnostics provided the funding for this work.

Conflict of interest

Jon Peterson was—and Marsha Oenick is—employed by and compensated by Ortho Clinical Diagnostics. Joseph Italiano and David Zurakowski were compensated as consultants to Ortho Clinical Diagnostics. No others have anything to disclose.

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Author notes

  1. Jon E. Peterson
    Present address: Salimetrics, LLC, State College, PA, 16803, USA

Authors and Affiliations

  1. Department of Research and Development, Ortho Clinical Diagnostics, 100 Indigo Creek Drive, Rochester, NY, 14626, USA
    Jon E. Peterson, Lea V. Michel & Marsha Oenick
  2. The Vascular Biology Program, Children’s Hospital Boston, Boston, USA
    Jon E. Peterson, Joseph E. Italiano Jr, Susan Connors, Robert J. D’Amato & Judah Folkman
  3. Department of Surgery, Harvard Medical School and Children’s Hospital Boston, Boston, MA, 02115, USA
    Jon E. Peterson, Joseph E. Italiano Jr, Susan Connors, Robert J. D’Amato & Judah Folkman
  4. Departments of Anesthesia and Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA
    David Zurakowski
  5. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
    Joseph E. Italiano Jr
  6. Department of Chemistry, Rochester Institute of Technology, Rochester, NY, 14623, USA
    Lea V. Michel
  7. Department of Ophthalmology, Harvard Medical School and Children’s Hospital Boston, Boston, MA, 02115, USA
    Robert J. D’Amato
  8. Division of Pediatric Hematology/Oncology, Pediatrics Department, Floating Hospital for Children, Tufts University School of Medicine, Boston, MA, 02111, USA
    Giannoula L. Klement

Authors

  1. Jon E. Peterson
  2. David Zurakowski
  3. Joseph E. Italiano Jr
  4. Lea V. Michel
  5. Susan Connors
  6. Marsha Oenick
  7. Robert J. D’Amato
  8. Giannoula L. Klement
  9. Judah Folkman

Corresponding author

Correspondence toJon E. Peterson.

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Peterson, J.E., Zurakowski, D., Italiano, J.E. et al. VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients.Angiogenesis 15, 265–273 (2012). https://doi.org/10.1007/s10456-012-9259-z

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