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Content archived on 2024-05-24

A paradigm for the establishment of new prognostic markers for common cancers: protease systems as indicators of invasive potential.

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Laminination signals tumour invasion

Different stages of cancer have their own molecular signature. Researchers in the EU-funded Proteases project have identified a protein that could act as a chemical indicator of the extent of tumour invasion.

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The progression of cancer is a complex web of cell and tissue remodelling. A series of molecular changes directs exactly which of the chemical pathways is going to occur. Doctors can therefore use the presence of particular molecules as markers to identify a stage of the cancer. Researchers with Proteases searched through the tumour cells of almost 100 patients with primary colon cancer to find suitable molecular candidates. Overall, the aim was to link a definite stage of the cancer with a certain amount of a marker. In the path to colon cancer invasion, two stages can be important to the oncologist – Dukes' stage and tumour budding. Dukes' stage is crucial because it marks the spread of the cancer beyond the inner lining of the colon to the lymph nodes outside this stretch of the large intestine. Small clusters of cells with no identity as yet lie ahead of the cancer at the tumour budding stage. As a reliable marker, one protein stood out as a candidate. Laminin-5 gamma 2 chain is part of the laminin family of proteins. As a group they are involved in a lot of important cell stages including development of cell type, differentiation, and signalling To see if laminin-5 gamma 2 chain was present, the cells were scored for presence of staining. Ratings for the amount of staining ranged from sparse, moderate to frequent. Normal cells were negative for the stain. In contrast, there was positive staining in 96% of the tumours. The link between frequency of staining for the laminin and the cancer stages held true. There was a very positive association between the presence of the gamma 2 chain protein and Dukes' stages A to C. The same level of correlation with tumour budding was observed. Overall, the study showed that the concentration of laminin-5 gamma 2 chain increases as the cancer progresses. Levels of the protein also rise as the disease becomes more aggressive. Stage of the cancer determines effective, timely treatment. A reliable marker for the extent of invasion of colon cancer has been identified. As this disease is the second most commonly occurring cancer in Europe, these findings are significant in the drive to improve the health of our ageing population.

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