PMID- 24945745 OWN - NLM STAT- MEDLINE DCOM- 20151013 LR - 20240322 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - Long-distance communication between laryngeal carcinoma cells. PG - e99196 LID - 10.1371/journal.pone.0099196 [doi] LID - e99196 AB - Tunneling nanotubes and epithelial bridges are recently discovered new forms of intercellular communication between remote cells allowing their electrical synchronization, transfer of second messengers and even membrane vesicles and organelles. In the present study, we demonstrate for the first time in primary cell cultures prepared from human laryngeal squamous cell carcinoma (LSCC) samples that these cells communicate with each other over long distances (up to 1 mm) through membranous tunneling tubes (TTs), which can be open-ended or contain functional gap junctions formed of connexin 43. We found two types of TTs, containing F-actin alone or F-actin and alpha-tubulin. In the LSCC cell culture, we identified 5 modes of TT formation and performed quantitative assessment of their electrical properties and permeability to fluorescent dyes of different molecular weight and charge. We show that TTs, containing F-actin and alpha-tubulin, transport mitochondria and accommodate small DAPI-positive vesicles suggesting possible transfer of genetic material through TTs. We confirmed this possibility by demonstrating that even TTs, containing gap junctions, were capable of transmitting double-stranded small interfering RNA. To support the idea that the phenomenon of TTs is not only typical of cell cultures, we have examined microsections of samples obtained from human LSCC tissues and identified intercellular structures similar to those found in the primary LSCC cell culture. FAU - Antanaviciute, Ieva AU - Antanaviciute I AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Rysevaite, Kristina AU - Rysevaite K AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; Institute of Anatomy, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Liutkevicius, Vykintas AU - Liutkevicius V AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Otorhinolaryngology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Marandykina, Alina AU - Marandykina A AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Rimkute, Lina AU - Rimkute L AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Sveikatiene, Renata AU - Sveikatiene R AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Uloza, Virgilijus AU - Uloza V AD - Department of Otorhinolaryngology, Lithuanian University of Health Sciences, Kaunas, Lithuania. FAU - Skeberdis, Vytenis Arvydas AU - Skeberdis VA AD - Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140619 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Actins) RN - 0 (Connexin 43) RN - 0 (Fluorescent Dyes) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (LST1 protein, human) RN - 0 (Membrane Proteins) RN - 0 (RNA, Small Interfering) SB - IM MH - Actins/metabolism MH - Carcinoma, Squamous Cell/*genetics/metabolism/pathology MH - Cell Communication/*genetics MH - Connexin 43/*metabolism MH - Fluorescent Dyes MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Laryngeal Neoplasms/*genetics/metabolism/pathology MH - Membrane Proteins/metabolism MH - Microtubules/metabolism MH - Mitochondria/metabolism/pathology MH - Nanotubes/chemistry MH - Optical Imaging MH - Permeability MH - RNA, Small Interfering/genetics/metabolism MH - Tissue Culture Techniques PMC - PMC4063716 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/20 06:00 MHDA- 2015/10/16 06:00 PMCR- 2014/06/19 CRDT- 2014/06/20 06:00 PHST- 2014/02/17 00:00 [received] PHST- 2014/05/12 00:00 [accepted] PHST- 2014/06/20 06:00 [entrez] PHST- 2014/06/20 06:00 [pubmed] PHST- 2015/10/16 06:00 [medline] PHST- 2014/06/19 00:00 [pmc-release] AID - PONE-D-14-07083 [pii] AID - 10.1371/journal.pone.0099196 [doi] PST - epublish SO - PLoS One. 2014 Jun 19;9(6):e99196. doi: 10.1371/journal.pone.0099196. eCollection 2014.