Download Tunneling nanotubes meso abstract

Tunneling nanotubes: How cancers can direct cellular content to target cells of the tumormicroenvironment
Background: Research efforts to understand communication mechanisms that influence cancer growth
and metastasis have been focused on gap junctions, exosomes and microvesicles, and cytokine signaling
interactions between cells. Currently there is limited understanding of how efficient cell-to-cell
communication occurs between distant cells in the complex tumor microenvironment. We propose
tunneling nanotube (TnTs) formation as an important and yet underexplored mechanism for cell-to-cell
communication in cancer. TnTs are thin, non-adherent actin filament-based open conduits that facilitate
cargo (proteins, mitochondria, and miRNA amongst others) transfer between numerous cell types. Lou
and colleagues who first imaged TnTs in solid tumors from patients with mesothelioma and lung cancer
using confocal imaging, provided support for TnTs in vivo. Our lab published data showing that tumorderived exosomes can stimulate as well as traffic between cells via TnTs. We hypothesize that tunneling
nanotubes can promote cell invasion and metastasis in our mesothelioma cell line model. Results: We
culture malignant pleural mesothelioma cells and quantified TnT formation for three days. Our findings
suggest that aggressive mesothelioma cells have a high rate of TnT formation. Interestingly, the rate of
formation was independent of cell proliferation and our non-cancerous cell line formed form TnTs at a
significantly lower rate. We are working to show evidence for cancer-stromal cell interaction via TnTs
from co-cultivation of an malignant cells with normal mesothelium and fibroblast. Conclusions: These
preliminary works suggest that aggressive malignant cells form significantly more TNTs than less invasive
cells. We also see similar results using other cancers (pancreatic, colorectal, and ovarian). We will
further explore these observations to provide evidence suggesting cancer cell to stromal interaction via
TNTs. In addition we look to identify factors that facilitate TNT formation and the impact on tumor
invasion and metastasis.