Liudmila Lobastova1, Dominik Kraus2, Alexander Glassmann3, Dilaware Khan4, Christian Steinhäuser4, Christina Wolff1, Nadine Veit1, Jochen Winter5, Rainer Probstmeier6. 1. Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany. 2. Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Bonn, Germany. 3. Life Science Inkubator, Bonn, Germany. 4. Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany. 5. Oral Cell Biology Group, Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany. 6. Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany. r.probstmeier@uni-bonn.de.
Abstract
PURPOSE: Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms. METHODS: The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed. RESULTS: Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %. CONCLUSIONS: Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.
PURPOSE:Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms. METHODS: The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed. RESULTS: Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %. CONCLUSIONS: Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.
Entities:
Keywords:
Collective cell migration; Gap junction; Rac; Single cell migration; Thyroid carcinoma
Authors: David Hecker; Joachim Kappler; Alexander Glassmann; Karl Schilling; Wolfgang Alt Journal: J Neurosci Methods Date: 2008-05-27 Impact factor: 2.390
Authors: Li Li; Robert Hartley; Bjoern Reiss; Yaohui Sun; Jin Pu; Dan Wu; Francis Lin; Trung Hoang; Soichiro Yamada; Jianxin Jiang; Min Zhao Journal: Cell Mol Life Sci Date: 2012-03-13 Impact factor: 9.261
Authors: Frank A H Meyer; Dominik Kraus; Alexander Glassmann; Nadine Veit; Jochen Winter; Rainer Probstmeier Journal: Int J Mol Sci Date: 2021-11-04 Impact factor: 5.923