Dynamics of cancerous tissue correlates with invasiveness

Ann-Katrine Vransø West,Joachim Mathiesen,Amalie Christensen,Jens Magelund Tarp,Lene Broeng Oddershede,Natascha Leijnse,Lena Wullkopf,Janine Terra Erler

doi:10.1038/srep43800

Ann-Katrine Vransø West, Joachim Mathiesen + Show 6 more

Open Access

https://doi.org/10.1038/srep43800

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Journal: Scientific Reports	Publication Date: Mar 1, 2017
Citations: 14	License type: open-access

Affiliation: University of Copenhagen

Abstract

Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

Highlights

The surrounding tissue, and this force is found to correlate with the invasiveness of the cancer
We investigated the human breast cancer cell lines MCF7 and MDA-MB-231
We investigated murine cell lines which exhibit the opposite phenotype with the non-invasive 67NR cells showing a more mesenchymal-like phenotype while the malignant 4T1s maintain a round epithelial shape. These differences are reflected in the gene-expression of the classical epithelial marker E-Cadherin: The invasive human breast cancer cell line MDA-MB-231 shows a striking downregulation of the cell adhesion protein E-Cadherin, while the invasive murine 4T1s maintain high E-Cadherin levels

Summary

Introduction

The surrounding tissue, and this force is found to correlate with the invasiveness of the cancer. We investigated the human breast cancer cell lines MCF7 (non-invasive) and MDA-MB-231 (invasive). We calculated the speed distributions of all investigated cell tissue types.

Results

Conclusion