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How polarisation helps tumour cells metastasise

An international research team identifies single-cell polarity as a feature of circulating tumour cells that helps cells to leave circulation and found metastases. The novel results provide a new potential target in the fight against metastatic cancer.

2018.02.28 | Lisbeth Heilesen

Polarised human melanoma cells in suspension. The picture to the left shows a fluorescence microscopic image showing polar distribution of the protein ezrin (displayed in yellow), and the actin cytoskeleton (displayed in magenta). The cell nucleus is shown in cyan. The picture to the right shows a thin section transmission electron microscopy image revealing strong polar folding of the plasma membrane, which makes the pole "sticky" and enhances cell attachment. Figure: Anna Lorentzen.

Metastasis, the spreading of cancer cells from a primary tumour often via lymph and blood circulation to different parts of the body, is the main course of death for cancer patients. Once in circulation, tumour cells are exposed to harsh conditions such as shear stress, blood pressure and attacks by immune cells. To exit the circulatory system, circulating tumour cells need to be able to attach to a vessel wall, firmly adhere, migrate through the vessel wall (transmigration) and through the tissue to establish a metastasis. During these migration steps, tumour cells need to rearrange their orientation and polarisation to form a front and back and determine their direction.

New research has discovered a novel type of polarisation of circulating tumour cells (termed single-cell polarity) that favours their attachment, adhesion and transmigration. Polarised cells are therefore able to leave the hostile environment of circulation faster than unpolarised cells, which increases their chance to establish metastases.

In this newly published study, Dr. Anna Lorentzen from the Department of Molecular Biology and Genetics, Aarhus University, together with researchers from Helmholtz Center Munich, the German Cancer Research Center Heidelberg and other collaborators have characterised single-cell polarity in various types of cancer cell lines and tumour cells isolated from cancer patients. They were able to show that cells use their "sticky" single-cell pole to directly attach to surfaces. In addition, the cells’ intrinsic polarisation orients the cellular machinery to advance firm adhesion and transmigration.

Using in vitro, in vivo and in silico methods, Lorentzen and her colleagues demonstrated that single-cell polarity correlates with metastasis of circulating tumour cells and that changes to cellular regulators of single-cell polarity led to reduced metastasis in mouse models. These studies provide a new potential target in the fight against metastatic cancer.

Future research is aimed at evaluating the clinical implications of these findings and providing further insight into the molecules that regulate single-cell polarity in order to identify potential targets for the treatment of metastatic cancer.

The results are published in the scientific journal Nature Communications entitled "Single cell polarity in liquid phase facilitates tumour metastasis”. DOI 10.1038/s41467-018-03139-6. 

For further information, please contact

Postdoc Anna Lorentzen
Department of Molecular Biology and Genetics, Aarhus University, Denmark
anna@mbg.au.dk - +45 87155478