Levels of activated platelet-derived microvesicles in patients with soft tissue sarcoma correlate with an increased risk of venous thromboembolism

Abstract

BackgroundMicrovesicles are small vesicles expressing specific antigens from their cells of origin. Elevated levels of microvesicles have been shown to be associated with coagulation disorders as well as with different types of malignancies. This study aims to evaluate a possible correlation of different microvesicle subpopulations with a positive history of venous thromboembolism (VTE) in patients with soft tissue sarcoma.MethodsAnnexin V - positive microvesicles, leukocyte (CD45-positive), platelet (CD61-positive), activated platelet (CD62P-, CD63-positive), endothelium-derived (CD62E-positive) and tissue-factor (CD142-positive) microvesicles were identified in the peripheral blood of patients with soft tissue sarcoma (n = 39) and healthy controls (n = 17) using fluorescence-activated cell sorting (FACS).ResultsBoth the total amount of Annexin V-positive microvesicles and levels of endothelium-derived (CD62E-positive) microvesicles were shown to decrease significantly after tumor resection (n = 18, p = 0.0395 and p = 0.0109, respectively). Furthermore, the total amount of Annexin V – positive microvesicles as well as leukocyte (CD45-positive) and endothelium-derived (CD62E-positive) microvesicles were significantly higher in patients with grade 3 (G3) soft tissue sarcoma (n = 9) compared to healthy controls (n = 17) (p = 0.0304, p = 0.0254 and p = 0.0357, respectively). Moreover, patients with G3 soft tissue sarcoma (n = 9) presented higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles compared to patients with grade 2 (G2) soft tissue sarcoma (n = 8) (p = 0.0483 and p = 0.0045). Patients with grade 1 (G1) soft tissue sarcoma (n = 3) presented with significantly lower levels of platelet (CD61-positive) microvesicles than patients with G3 soft tissue sarcoma (n = 9) (p = 0.0150).In patients with a positive history of VTE (n = 11), significantly higher levels of activated platelet (CD62P- and CD63-positive) microvesicles (p = 0.0078 and p = 0.0450, respectively) were found compared to patients without a history of VTE (n = 28).ConclusionWe found significantly higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles to be circulating in the peripheral blood of patients with G3 soft tissue sarcoma compared to patients with G2 soft tissue sarcoma. Furthermore, we showed that high counts of activated platelet-derived microvesicles correlate with the occurrence of VTE. Thus, the detection of these microvesicles might be an interesting new tool for early diagnosis of soft tissue sarcoma patients with increased risk for VTE, possibly facilitating VTE prevention by earlier use of thromboprophylaxis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3515-y) contains supplementary material, which is available to authorized users.

Platelets and Metastasis: New Implications of an Old Interplay

“…In contrast, a growing body of literature on PMPs supports their potential contribution to VTE in cancer patients. Previous reports have shown increased plasma levels of PMPs in cancer patients vs. healthy controls, with increased levels correlated with tumor grade (254)(255)(256). Importantly, high plasma PMP levels are correlated with poor overall survival from prostate cancer and higher risk of metastasis in both prostate and gastric cancer, where PMPs can be used as predictors of metastatic disease with high sensitivity and specificity (255,257).…”

“…Cancer patients with a history of VTE have higher plasma levels of PMPs than cancer patients with no prior VTE events (113,256). These vesicles are derived from both resting and activated platelets and only a minority expressed TF (113,256). Importantly, Bucciarelli et al observed that PMPs could be an independent predictor of overall VTE risk, supporting the use of PMPs as a biomarker to identify patients at high risk of VTE, with or without cancer.…”

“…Importantly, high plasma PMP levels are correlated with poor overall survival from prostate cancer and higher risk of metastasis in both prostate and gastric cancer, where PMPs can be used as predictors of metastatic disease with high sensitivity and specificity (255,257). Cancer patients with a history of VTE have higher plasma levels of PMPs than cancer patients with no prior VTE events (113,256). These vesicles are derived from both resting and activated platelets and only a minority expressed TF (113,256).…”

Extracellular Vesicles: Packages Sent With Complement

“…Supporting this, MV-bound TF can be detected in a variety of diseases, including trauma, sepsis, and cancer ( 35 , 36 ). This so-called “blood-borne” TF may contribute to the development of thrombosis that is associated with these diseases ( 36 – 39 ).…”

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

“…As particles naturally secreted from the cell, EV has been identified as vital mediators of paracrine communication (Batiz et al, 2015;Jing et al, 2018) and demonstrated a key role in different processes, such as angiogenesis (Qi et al, 2016), antigen presentation (Shenoda and Ajit, 2016), apoptosis (Qi et al, 2019), coagulation (Fricke et al, 2017), cellular homeostasis (Takahashi et al, 2017), inflammation (Zhang S. et al, 2019).…”