Abstract
Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs). TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined changes in TnT length over time in comparison to cell proliferation. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo.
Highlights
Malignant pleural mesothelioma (MPM) is a clinically devastating and locally invasive malignancy
To determine whether tunneling nanotubes (TnTs) formation occurs at a higher rate in malignant mesothelioma cells than in benign cells, we cultured the MPM cell lines H2052, VAMT, and MSTO-211H and the benign mesothelial cell line MeT5A
Cells were cultured in medium that we previously demonstrated induces TnT formation (Lou et al, 2012b)
Summary
Malignant pleural mesothelioma (MPM) is a clinically devastating and locally invasive malignancy. Patients with this disease uniformly carry a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. The proportion is highest in biphasic and sarcomatoid tumors, the latter of which is associated with even worse prognosis than other subtypes (Motta et al, 2006). This tumorstroma balance creates a heterogeneous microenvironment composed of, among other things, malignant cells, cancer-associated fibroblasts, vascular endothelial cells, macrophages, and other inflammatory infiltrates. In a study of MPM, inflammatory or www.frontiersin.org
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