gms | German Medical Science

Introduction: Tunneling nanotubes (TN) and epithelial bridges are recently discovered new form of intercellular communication between remote cells allowing their electrical synchronization, transfer of second messengers, vesicles and even organelles. The aim of this study was to examine the modes of formation of TNs between laryngeal squamous cell carcinoma (LSCC) cells and to describe their structure as well as electrical and permeability properties.

Methods: Primary LSCC cell culturing, immunofluorescence analysis of LSCC cells and tissues, dual whole-cell patch-clamp measurements, and time-lapse imaging were performed.

Results: It was demonstrated for the first time, that LSCC cells in culture communicate with each other over long distances (up to 1 mm) through membranous TNs that can be open-ended or contain functional gap junctions formed of connexin 43. Two types of TNs, containing F-actin alone or F-actin and α-tubulin, were identified. Five modes of TNs formation were characterized. The longest open-ended TNs formed during cytokinesis. TNs that formed by lamellipodia or filopodia outgrowth mechanism established the intercellular communication through gap junctions. TNs coupled the remote cells electrically and metabolically, and were capable of transporting mitochondria and transmitting double-stranded small interfering RNA. Finally, the intercellular structures similar to those in cell culture were demonstrated in microsections of LSCC tissue samples.

Conclusions: Results of the present study contribute to better understanding of intercellular communication between LSCC cells providing more definite conception on mechanisms of tumor growth and spreading.

Unterstützt durch: Grant No. LIG-13/2012 from the Research Council of Lithuania

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