Oral Squamous Cell Carcinoma Is Associated with a Low Thrombosis Risk Due to Storage Pool Deficiency in Platelets.

Pierre Haen,Lydie Crescence,Diane Mege,Christophe Dubois,Laurence Panicot-Dubois,Alexandre Altié

doi:10.3390/biomedicines9030228

Abstract

Venous thrombo-embolism (VTE) disease is the second most common cause of mortality in cancer patients, and evaluation and prevention of thrombosis risk is essential. VTE-associated risk varies according to the type of tumor disease. Oral cancer is the most frequent type of head and neck cancer, and it represents approximately 2.1% of all cancers worldwide. Most tumors are squamous cell carcinomas and are mainly due to tobacco and alcohol abuse. VTE risk associated with oral squamous cell carcinoma (OSCC) is low. However, many studies have shown that OSCC has the following biological features of cancers associated with a high thrombosis risk: modified thrombosis and fibrinolysis mechanisms; strong expression of procoagulant proteins; secretion of procoagulant microparticles; and production of procoagulant cytokines. Using an original mouse model of tongue squamous cell carcinoma, our study aimed to clarify this paradoxical situation. First, we showed that OSCC tumors have a pro-aggregatory phenotype and a high local thrombosis risk. Second, we found that tongue tumor mice do not have an elevated systemic thrombosis risk (the risk of an “at distance” thrombosis event such as lower extremity deep venous thrombosis or pulmonary embolism) and even show a reduction in risk. Third, we demonstrated that tongue tumor mice show a reduction in platelet reactivity, which explains the low systemic thrombosis risk. Finally, we found that tongue tumor mice present granule pool deficiency, thereby explaining the reduction in platelet reactivity and systemic thrombosis risk.

Highlights

The association between venous thrombo-embolism and malignancy was first described by Bouillaud and Trousseau [1,2] in the 19th century
Thrombosis risk associated with oral squamous cell carcinoma (OSCC) has been empirically shown to be low or nonexistent [9,10]. This risk is demonstrable [11,12], and many studies have shown that OSCC has the following biological features of cancers associated with a high thrombosis risk: modified thrombosis and fibrinolysis mechanisms [13,14]; strong expression of procoagulant proteins, such as factor tissue (FT) [15,16]; secretion of procoagulant microparticles [17]; and production of procoagulant cytokines [18]
To investigate the ability of OSCC cells to induce platelet aggregation, we evaluated murine platelet aggregation after adding suspended AT-84 cells in serum free to RPMI

Summary

Introduction

The association between venous thrombo-embolism and malignancy was first described by Bouillaud and Trousseau [1,2] in the 19th century. It has been clearly shown that the association exists for a hypercoagulable state associated with malignancy and that thrombosis risk differs according to the cancer features (histological features, localization, and stages) and cancer treatments used (chemotherapy, surgery, and radiotherapy) [3]. Venous thrombo-embolism disease, especially pulmonary embolism, is the second most common cause of mortality in cancer patients. Evaluation and prevention of thrombosis risk is essential [4]. Anticoagulant therapy is indicated in the prevention of venous thromboembolism (VTE), but its use must be limited in high-risk patients because it may be responsible for complications, such as hemorrhage or immuno-allergic reactions [3].

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Results

Conclusion