Vasculogenic mimicry in vitro in tumour cells derived from metastatic malignant pleural effusions

Malignant pleural effusions (MPEs) are most commonly caused by advanced metastatic malignancy, with an average survival time of 3–12 months post-diagnosis.1 The pathogenesis of MPEs is not fully understood, but impaired fluid drainage by blood or lymphatic vessels, inflammation and increased vascular permeability are known to contribute. More recently, angiogenesis has been recognised as playing a role in the development of MPEs, and vascular endothelial growth factor (VEGF), which drives vascular development, is a recognised prognostic factor. Anti-angiogenic therapies directed at VEGF may improve effusion control in some settings.1, 2 However, anti-VEGF therapy has limited effects on vasculogenic mimicry (VM), the process by which tumour cells differentiate into vascular endothelial-like cells to form new vascular networks.3 VM has been identified in 36% of lung4 and 20–30% of primary breast carcinomas;5 lung and breast carcinomas are the most common causes of MPEs. In a meta-analysis of 3062 cases, Cao et al. associated VM with poor patient survival (31% 5 year overall survival in VM positive patients, compared to 56% in VM negative patients).6 Effusions are routinely drained for patient comfort and diagnosis, and provide a source of patient-derived primary tumour cells that could be used to characterise tumour cell behaviour to optimise therapy. We have previously shown that mesothelioma cells harvested from MPEs display VM in vitro, whereas previous studies have focussed on the use of primary tumour cells to predict chemotherapy sensitivity.7 Here, we demonstrate that effusion-derived tumour cells display VM and could be used to test therapy response.