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Cancer cell motility: lessons from migration in confined spaces

Nature Reviews Cancer volume 17, pages 131–140 (2017)Cite this article

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Abstract

Time-lapse, deep-tissue imaging made possible by advances in intravital microscopy has demonstrated the importance of tumour cell migration through confining tracks in vivo. These tracks may either be endogenous features of tissues or be created by tumour or tumour-associated cells. Importantly, migration mechanisms through confining microenvironments are not predicted by 2D migration assays. Engineered in vitro models have been used to delineate the mechanisms of cell motility through confining spaces encountered in vivo. Understanding cancer cell locomotion through physiologically relevant confining tracks could be useful in developing therapeutic strategies to combat metastasis.

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Figure 1: Microenvironments for confined migration in vivo.
Figure 2: Determinants of cell migration in confinement.

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Acknowledgements

The authors gratefully acknowledge support from the US National Institutes of Health (grants R01CA183804, R01CA186286, R01GMS114675 and U54CA210173).

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Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering and the Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, 21218, Maryland, USA

    Colin D. Paul, Panagiotis Mistriotis & Konstantinos Konstantopoulos

  2. Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, 21218, Maryland, USA

    Konstantinos Konstantopoulos

Authors
  1. Colin D. Paul
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  2. Panagiotis Mistriotis
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  3. Konstantinos Konstantopoulos
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Correspondence to Konstantinos Konstantopoulos.

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PowerPoint slides

Glossary

3D longitudinal tracks

Tunnel-like spaces in which cells are confined either at their basal and apical surfaces or around their periphery, but encounter open space at the cell front and rear.

Collective migration

Cell migration in which groups of cells migrate while in physical contact and in the same net direction. This is in contrast to single cell migration in which cells move individually and are not in physical contact with other motile cells.

Contact guidance

The tendency of cells (or groups of cells) to align and polarize along topographical features, such as microchannel walls or aligned collagen fibres.

Contact inhibition

The tendency of cells to suppress forward movement upon leading-edge contact with another cell.

Matrix metalloproteinases

(MMPs). Soluble or membrane bound enzymes that sever extracellular matrix proteins to mediate matrix remodelling, cell migration or cell signalling.

Organ-on-a-chip

Engineered devices that attempt to recapitulate the major functions and anatomical organization of an organ on a miniaturized scale.

Polydimethylsiloxane

(PDMS). A silicone rubber polymer that is frequently used to fabricate microfluidic devices. PDMS is optically transparent, allows diffusion of oxygen and can be coated with various extracellular matrix proteins to promote cell adhesion.

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Paul, C., Mistriotis, P. & Konstantopoulos, K. Cancer cell motility: lessons from migration in confined spaces. Nat Rev Cancer 17, 131–140 (2017). https://doi.org/10.1038/nrc.2016.123

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