Editors' ChoiceCancer

The tip of the thrombos-is-berg

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Science Translational Medicine  01 Feb 2017:
Vol. 9, Issue 375, eaam6053
DOI: 10.1126/scitranslmed.aam6053

Abstract

A high risk of venous thromboembolic events is just one of the challenges faced by people with malignant brain tumors.

Malignancy is a major risk factor for venous thromboembolic events (VTEs) in adults, but the mechanisms for this are not well understood. Potential contributors include central venous catheters and hematogenous tumor metastasis. Patients with brain tumors have additional risk factors, including immobility due to the tumor itself or to the effects of tumor resection. Unfortunately, regardless of the cause, VTEs during malignancy increase mortality risk.

Riedl and colleagues investigated potential mechanisms of VTEs in a single-center prospective cohort study of patients with primary brain tumors, mostly high-grade gliomas. High-grade gliomas are the most common brain tumors in adults and have very poor long-term survival, with fewer than 20% of patients surviving for 5 years after diagnosis. The authors used immunohistochemistry to evaluate expression of podoplanin, a platelet-activating protein, in brain tumor specimens. They found that high podoplanin expression on tumor biopsy specimens correlated with more platelet aggregates in intratumor blood vessels. In cell culture, a high-grade glioma cell line with high podoplanin expression induced platelet activation and aggregation, whereas a tumor cell line that lacked podoplanin expression did not. Furthermore, patients whose tumors had higher podoplanin expression had lower peripheral blood platelet counts and higher D-dimer concentrations, suggesting in vivo coagulation activation, and these patients had more VTEs and higher mortality rates within two years. Last, treatment of glioma cell cultures with an anti-podoplanin antibody abrogated the formation of platelet aggregates, suggesting a potential therapeutic target.

Although this study identified brain tumor podoplanin expression as a risk factor for VTEs, several questions remain. The authors note that podoplanin expression is higher in more invasive gliomas, acknowledging that glioma progression is the major cause of mortality. It is conceivable that blocking podoplanin activity may limit tumor invasion as well as VTEs, but the clinical feasibility and efficacy of this approach remains to be seen. Given the poor prognosis for patients with high-grade brain tumors, more translational research is critically needed.

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