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

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/10(6), PF4 18.5 versus 9.4 ng/10(6), and PDGF 34.1 versus 21.0 pg/10(6). 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.

Evidence against a role for platelet-derived molecules in liver regeneration after partial hepatectomy in humans

“…These findings are in accordance with previous work that showed an increase in the levels of angiogenic proteins in platelets but not in plasma in both mouse models of cancer and in patients with cancer [37,38]. The consistently lower postoperative levels of the anti-angiogenic endostatin in patients undergoing partial hepatectomy as compared to the PPPD patients is of interest and may reflect the requirement for angiogenesis in the partial hepatectomy group.…”

Plasma molecules predicting liver dysfunction following partial hepatectomy are not only derived from platelet α‐granules

“…The higher preoperative levels of VEGF in platelets (but not in plasma) compared to controls is consistent with the reported selective increase in VEGF in platelets from patients with colorectal cancer. (6) Bars represent means; error bars indicate standard error of the mean. *P < 0.01.…”

Ex vivoDetermination of an Estradiol Analogue-Induced Changes on Platelet Morphology and Angiogenic Biomarkers

“…PDGF-α and -β Expression of PDGFR-αhas been noticed in subtypes of mesenchymal progenitors in the lungs, skin, and intestine (Peterson et al, 2012). PDGFR-β is expressed in mesenchyme, particularly in vascular SMCs and pericytes (Andrae et al, 2008).…”

“…Platelets have been associated with malignant diseases since the late 19th century (Jain et al, 2010;Sabrkhany et al, 2011;Peterson et al, 2012). It has been hypothesized that tumors promote platelet activation and aggregation by expressing or releasing platelet-activating factors such as tissue factor, thrombin, and adenosine diphosphate (ADP) (Sabrkhany et al, 2011).…”

“…Angiogenesis-regulating proteins are involved in the progression of tumors (Peterson et al, 2012). These proteins are thus ideal biomarkers in studying pathophysiology of tumors by investigating the role of angiogenesis regulatory factors in platelets, lymphocytes, and erythrocytes.…”