Cancer Stem Cells


The recent discovery of human embryonic stem cells and of multipotent adult progenitor cells, which can be experimentally led to differentiate into a wide range of cell types has strongly increased the interest in stem cell biology. It is only recently that a clear link has been established between stem cells and cancer in a variety of tumour types since tumours often arise from the transformation of normal stem cells. Moreover it has been shown in several instances that solid tumours contain a small proportion of cancer stem cells (CSCs) and that these CSCs are responsible for the tumour phenotype. The proliferative, self-renewal and differentiation properties of these CSCs are reminiscent of normal stem cells, suggesting that they may behave similarly when placed in presence of the same signals.
To our knowledge, only a few studies have been focused on CSCs. Notably, Singh and collaborators (2003) and Hemmati and collaborators (2003) have isolated and characterized brain tumour stem cells from medulloblastoma, ganglioglioma, astrocytoma and ependymoma tumours isolated from children. A recent review also discusses the presence of stem cells in brain tumours (Oliver and Wechsler-Reya, 2004).
In another type of approach, van de Wetering and co-workers (2002) in H. Clevers’s lab have demonstrated that by turning off the Wnt signalling pathway, which is constitutively active in colorectal cancer cells, they could trigger in vitro the differentiation of the transformed colon cancer cells into differentiated, non-proliferative, colonic cell types.
This shows that the Wnt signal is a Master Switch for the control of colon cancer and that it is possible to knock cancer cells off their proliferative “vicious” circle and trigger their differentiation leading to a non-cancerous phenotype.

Brain Cancer Stem Cells & Differentiation Factors

We propose to investigate CSCs and to identify and use the Master Switch factors responsible for the choice between proliferation and differentiation. We hope that this will lead to a change of paradigm in the treatment of cancers. The proposed approach is illustrated below:

We are presently carrying research to be able:

  • To generate and isolate cancer stem cells from human brain tumours
  • To identify the secreted Switch factors required for the differentiation of these cancer stem cells
  • To differentiate efficiently these stem cells into post-mitotic neurons and glial cells by the addition of a Switch factor or a combination thereof.
  • To differentiate in vitro tumourspheres derived from CSCs


Biomarkers for brain Cancer Stem Cells

Development of new diagnostic and prognosis tools for human glioblastoma cancer stem cells

It has been recently shown that cancer is frequently a stem cell disorder in which uncontrolled proliferation of cancer stem cells (also called Brain Tumour Initiating Cells, BTICs) is at the origin of tumor growth and development.


We aim at identifying and visualizing the cancer stem cells present at low frequency in brain tumors. To achieve this aim, we will generate single-domain antibody fragments recognizing  a known brain cancer stem cell biomarker (CD133).
These will be used to detect with a high specificity the presence of cancer stem cells in brain tumors and biopsies isolated during surgical treatment. This technique may be extended to other tumors characterized by the expression of the same biomarker (ovarian, liver and gastric cancers).

This should lead to the development of diagnostic and prognosis tools that will be used to improve the treatment of the cancer patients. The initial target group is patients with glioblastoma brain tumors that represent about 50% of all brain tumors and are found in 2 to 3 cases per 100 000 persons.

This project is financed by the Fournier-Majoie Foundation (see website: FFMI).



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