This talk was the most interesting for me maybe from the entire annual 2010 AACR meeting. Because it made me to look at cancer stem cell concept from other side – side of cancer non-stem cells.
Carlo Maley applied principles of evolution and natural selection to tumor populations and highlighted a paradox of cancer stem cell rarity or why non-stem cells persist. He asked why cancer stem cell remain rare, if natural selection should lead to complete domination of this population of entire neoplasm. For example, we should expect increasing proportion of cancer stem cells with serial transplantation and also in “older” neoplasms compared to “young”, but it’s not tested yet. He proposed the theory of proto-multicellularity in neoplasm. According this theory cancer stem cells cooperate with cancer non-stem cells which benefit neoplasm evolution overall. He proposed to call cancer stem cells – cancer germ-line cells and cancer non-stem cells – cancer somatic cells.
Carlo Maley is a professor at the Wistar Institute, Philadelphia.
Some interesting thoughts from his talk:
- – natural selection should lead to neoplasms dominated almost completely by cancer stem cells but we don’t see that; this is a paradox of rare cancer stem cells;
– hierarchy of cancer stem cells is an assumption which should be tested further;
– current assays confound engraftment with stemness;
– it is possible that self-renewing cells not able to engraft very well in immunocompromised mice and we can miss them;
– having surface cancer stem cell markers doesn’t tell you much (as much as you think) about self-renewal capacity;
– we should test how much propensity to self-renew heritable or controlled by microenvironment;
– cancer non-stem cells have fitness effect on cancer stem cells, such as: niche-stroma and supression of competitors, they must co-exist;
– cooperation between cancer germ cells and cancer somatic cells leads to a selection at a new level = proliferative units.