Differential changes in platelet VEGF, Tsp, CXCL12, and CXCL4 in patients with metastatic cancer

Abstract

Data from animal studies indicate that platelets play a key role in tumor dissemination and metastasis. We therefore hypothesized that metastastic cancer patients may display a specific platelet phenotype. Percentage of activated, p-selectin positive platelets as well as platelet contents (i.e., plasma and platelet count-corrected serum levels of VEGF-A, CXCL12, CXCL4, and thrombospondin-1) were analyzed in 43 patients with newly diagnosed metastatic disease prior to treatment. Tumor patients had increased platelet counts and significantly elevated percentages of activated platelets. Moreover, the platelet content of VEGF-A in cancer patients was significantly increased compared to healthy controls, while thrombospondin-1, CXCL12 and CXCL4 were significantly decreased. Our data contain several unexpected results: firstly, CXCL12 was found in minute quantities in the serum as compared with murine studies. Secondly, CXCL4, which was found by mass spectrometry to be the single massively upregulated intraplatelet chemokine in mice after tumor xenotransplantation, was decreased in tumor patient platelets. While increased contents of VEGF-A have been attributed to platelet scavenger activity, the differential decrease of specific platelet contents may be due to differential secretion or altered megakaryopoiesis in metastatic cancer patients.

Fluorescence Nanoscopy of Platelets Resolves Platelet‐State Specific Storage, Release and Uptake of Proteins, Opening up Future Diagnostic Applications

“…Studies on mice bearing human malignant tumour xenografts have shown that circulating platelets can specifically sequester angiogenesis regulatory proteins strongly correlated to micrometastasis, even in the presence of very small tumours (< 1mm 3 ) and when no significant change in the plasma content of the same angiogenesis regulatory proteins can be observed [6] . Similar alterations, representing a "metastatic/malignant platelet phenotype" has also been seen in patients with different, newly diagnosed metastatic diseases, displaying both increased and decreased platelet contents of specific, in particular angiogenesis regulating proteins [7] . This suggests that tumour-associated alterations in the protein content in platelets can be valuable biomarkers for early cancer progression.…”

Elevated Serum Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Could be Useful in Lung Cancer Diagnosis

“…There is a direct correlation between the number of circulating platelets and the level of serum VEGF (Benoy et al, 2002). In addition, Wiesner et al reported that; the platelet content of VEGF-A was significantly elevated in cancer patients compared to controls (Wiesner et al, 2010). In another pathway.…”

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…Platelets in patients with newly diagnosed metastatic disease display an activated state measured by P-Selectin expression (12), indicating that these cells are potentially an important factor in tumor metastasis. A study by Wang and Zhang (13) using various tumor cell lines suggested that platelets directly influence tumor cell proliferation in an MHC-independent manner.…”

“…Both clinical and experimental evidence point to a role of platelets in the spread of cancer, as thrombocytopenia or anti-platelet treatments ameliorate experimental metastasis, and tumors provide a thrombogenic proinflammatory environment that promotes coagulation and endothelial cell activation (10,11). Interestingly, patients with metastatic disease reveal increased platelet counts and significantly elevated numbers of activated platelets (12). Depending on the type of tumor, various aspects of cancer progression may be affected by platelets, including tumor cell proliferation (13), tumor angiogenesis (14), vessel stability within tumors (15), or immune evasion (16,17).…”