Lineage tracing for identification of cancer stem cells

by Alexey Bersenev on August 1, 2012 · 0 comments

in cancer, methods

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Lineage tracing analysis is sophisticated method of genetic labeling that allows identification of progeny of cell ancestor. For the first time lineage tracing (clonal analysis) was successfully used for identification of cancer stem cells (CSC). Three independent groups have published their findings in Nature (1/2) and Science.

Lineage tracing have been used in stem cell research for many many years. The most elegant studies were done by Hans Clevers group on mouse intestine stem cells. It was a great complement to transplantation assays. Application of lineage tracing techniques in cancer stem cell research was the next logical step. Unlike normal stem cell, application of transplantation assays in cancer stem cell field caused a lot of controversies. Transplantation assays techniques include a great manipulation of different cell populations outside the context of natural environment. Moreover, the use of immunocompromised mice in transplantation assays, adding more complexity and artificiality in the model. Lineage tracing studies provided evidence for the existence of CSC in natural unperturbed tumor.

Read summaries and expert’s opinions:
Cancer stem cells tracked (Nature News)
Cancer stem cells can fuel tumor growth (Science Now)
Cancer stem cells really do exist? (The Scientist)

Two quotes from Nature commentary:

The three papers represent an important new chapter in the debate over CSCs. They introduce us for the first time to these cells in their native habitats and provide the first hard evidence that such cells are a legitimate therapeutic target. The next steps will include determining how well mouse CSCs recapitulate their human counterparts, and how best to destroy these for the benefit of patients.

Besides the proof of CSC existence and methodological advance, these studies provided a new insight in tumor growth dynamics:

The authors found neutral competition between CSCs; that is, every CSC within a tumour is equally likely to clonally expand or die off, probably even in the absence of new mutations (Fig. 1b). Their observations suggest that clonal expansion is a continuous process in tumours, not a rarity driven by a new, selectively advantageous mutation. And the results place competition between tumour cells at the centre of cancer evolution. In this context, mutations that simply drive proliferation may be of less importance than previously thought, whereas mutations that slightly tip the balance of competition to favour one CSC over another — perhaps by improving survival, promoting self-renewal or monopolizing limited resources — might be the ones that are highly selected in tumours.

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