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Cellular Oncology

, Volume 40, Issue 1, pp 63–76 | Cite as

Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates

  • Liudmila Lobastova
  • Dominik Kraus
  • Alexander Glassmann
  • Dilaware Khan
  • Christian Steinhäuser
  • Christina Wolff
  • Nadine Veit
  • Jochen Winter
  • Rainer ProbstmeierEmail author
Original Paper

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.

Keywords

Collective cell migration Gap junction Rac Single cell migration Thyroid carcinoma 

Notes

Acknowledgments

This research was supported by the Deutsche Forschungsgemeinschaft (STE 552/4, STE 552/5; to C.S.) and EU EraNet NEURON (Project BrIE; to C.S.).

Compliance with ethical standards

Conflict of interest

None declared.

Supplementary material

13402_2016_305_MOESM1_ESM.mov (511 kb)
Movie 1 Single cell migration of B-CPAP cells on untreated cell culture plastic. (MOV 511 kb)
13402_2016_305_MOESM2_ESM.mov (661 kb)
Movie 2 Single cell migration of FTC-133 cells on a fibronectin-covered surface. (MOV 661 kb)
13402_2016_305_MOESM3_ESM.mov (584 kb)
Movie 3 Single cell migration of FTC-133 cells on a laminin-covered surface. (MOV 583 kb)
13402_2016_305_MOESM4_ESM.mov (2.6 mb)
Movie 4 Collective cell migration: Typical migration pattern of a FTC-133 cell sheet. (MOV 2619 kb)
13402_2016_305_MOESM5_ESM.mov (1.9 mb)
Movie 5 Collective cell migration: Integration of an isolated FTC-133 cell into a migrating cell sheet. (MOV 1934 kb)
13402_2016_305_MOESM6_ESM.mov (2 mb)
Movie 6 Collective cell migration: Emigration of a single B-CPAP cell out of a migrating cell sheet. (MOV 2069 kb)
13402_2016_305_MOESM7_ESM.mov (703 kb)
Movie 7 Collective cell migration: Mobility potential of B-CPAP cell aggregates. (MOV 703 kb)

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Copyright information

© International Society for Cellular Oncology 2016

Authors and Affiliations

  • Liudmila Lobastova
    • 1
  • Dominik Kraus
    • 2
  • Alexander Glassmann
    • 3
  • Dilaware Khan
    • 4
  • Christian Steinhäuser
    • 4
  • Christina Wolff
    • 1
  • Nadine Veit
    • 1
  • Jochen Winter
    • 5
  • Rainer Probstmeier
    • 1
    Email author
  1. 1.Neuro- and Tumor Cell Biology Group, Department of Nuclear MedicineUniversity Hospital BonnBonnGermany
  2. 2.Department of Prosthodontics, Preclinical Education, and Material ScienceUniversity of BonnBonnGermany
  3. 3.Life Science InkubatorBonnGermany
  4. 4.Institute of Cellular Neurosciences, Medical FacultyUniversity of BonnBonnGermany
  5. 5.Oral Cell Biology Group, Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany

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