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FP6

MCSCS — Result In Brief

Project ID: 37297
Funded under: FP6-LIFESCIHEALTH
Country: Netherlands

Unravelling the profile of migrating cancer stem cells

Targeting cancer stem cells (CSCs) is believed to be the way forward for combating cancer. Leading European scientists in the field worked to elucidate the profile and function of CSCs in colon and breast cancer.
Unravelling the profile of migrating cancer stem cells
The idea that cancer establishment and maintenance is a result of a small subpopulation of cells, the CSCs, was introduced in the late 1990s. Research over the years has shown that CSCs are not only responsible for local invasion and distant metastasis but for drug resistance and remission as well. Despite the enormous scientific contribution, our understanding of the profile of CSCs remains limited, hampering the development of tailor-made anti-cancer therapies.

The primary objective of the EU-funded project ‘Migrating cancer stem cells in breast and colon cancer’ (MCSCS) was to understand the function, regulation and evolution of migrating CSCs in a multicellular organism. To achieve this, project partners used animal models to identify and isolate breast and colon MCSCs and eventually translated the results on large collections of human cancers.

Among the project objectives was to define a 'MCSC signature'; in other words, to identify the key characteristics of these cells in order to develop future tailor-made therapeutic approaches. One of the key features of both intestinal and mammary cancer was an activated Wnt signalling pathway, clearly demonstrating that its effector molecule, beta catenin, represents a functional marker of CSCs. An additional MCSC feature was the gene ZEB1 which was found to make CSCs more oncogenic by upregulating certain stem cell factors.

Researchers also discovered that epigenetic modifications in the genome of MCSCs were instrumental in defining the profile of these cells and could potentially serve as therapeutic targets. They concluded that in order to elucidate the functional heterogeneity of MCSCs, a combination of genomic, gene expression and cell surface antigen analyses is required. Finally, human cell models were generated carrying targeted mutations in genes known to play rate-limiting roles in CSCs. These were used to perform pharmacogenomic analyses and identify genotype-drug–specific relationships which could help the development of CSC-targeted therapies.

MCSCS project findings made a significant contribution to the understanding of biology and function of intestinal and breast CSCs. Understanding how these cells establish the original tumour and contribute to metastatic disease will help design more effective anti-cancer therapies.

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