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FP7

Metastasis Sys Mod Result In Brief

Project ID: 268278
Funded under: FP7-PEOPLE
Country: Israel

Cell motility signalling and metastasis

Migration of tumour cells from primary sites leads to formation of metastases and poor disease prognosis. Investigation of cancer cell motility may greatly benefit the development of new therapeutic methods.
Cell motility signalling and metastasis
Cell motility is associated with the formation of distinct types of protrusions or invaginations of cell membrane. In addition, cells display less-studied structures called membrane blebs. Blebs are large, round protrusions of the cell surface, driven by detachment from the underlying layer of structural proteins, the actin cortex. Recent evidence supports a central role for membrane blebbing in cell migration and cancer metastases.

The cell signalling that regulates bleb formation and retraction is poorly understood. The EU-funded METASTASIS SYS MOD (System level modelling of metastasis from signalling to cell motility) project investigated the signalling in blebbing and cell migration using experimental data and computer simulation.

Experimental data were obtained using wild-type and different mutants of HEK293T cells. Researchers found that overexpression of tyrosine kinase Met, implicated in tumorigenesis, correlated with an increase in blebbing rate. Experimental overexpression of other proteins involved in Met-induced signalling also showed increased blebbing in cell-based experiments.

Researchers created a mathematical model for cellular blebbing to analyse the signalling modifications and the resulting changes in the cell shape. The model represents the plasma membrane, the cell cortex and the forces on each of them as well as between them. A break of the membrane attachment to the cortex leads to a cytoplasmic burst of the hydrostatic pressure and to the bleb formation. A reconnection between the membrane and the cortex then leads to the bleb retraction.

The model has been tested and verified by comparison with experimental observations. Observations indicated it represented a potentially useful tool for identification of the molecules involved in the process of membrane and cortex reconnection and bleb retraction.

Finally researchers included metabolism and cell proliferation into an elaborated mathematical simulation of the metastatic process. Using data-based modelling for motility, invasion, proliferation and metabolism they analysed combinations which increase cancer’s ability to metastasise. Analysis demonstrated that co-existence of different cell clones in the tumour increases its metastatic ability in a changing environment.

The model also highlighted the crucial role of cell metabolism in the metastatic process. The researchers indicate that this could be a useful avenue for research into drug targets.

Related information

Keywords

Cell motility, signalling cancer, metastases, cell blebs
Record Number: 180930 / Last updated on: 2016-03-30
Domain: Biology, Medicine
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