My thoughts on the evolution of a differentiated tumor cell to cancer stem cell

In an earlier comment on my blog, I mentioned about how the "Dolly effect" may possibly result in the generation of cancer stem cells. In the milieu within a tumor mass, an evolutionary fight for survival is being waged. Tumor cells are described according to their grade. Lower grade tumors (grade 1 and grade 2) are more differentiated vis-a-vis higher grade tumors (National Cancer Institute).

It's tempting to suggest an experimental approach in vitro to simulate a sequence of events that may result in the generation of cancer stem cells from differentiated cells. The scarcity of nutrients within a rapidly growing tumor mass makes the acquisition of the ability to metastasize a selective advantage. Acquiring the cancer stem cell phenotype is a step to attaining the advantage. In my suggested approach, Wnt and notch pathways can be constitutively activated through stable transfection of differentiated tumor cells. Constitutively active beta catenin can be transfected to achieve constitutive Wnt/beta catenin signaling (Baba et al, 2006). Similarly, the constitutively active form of Notch, the Notch Intracellular domain (NICD) can be transfected into cell-lines (Purow et al, 2005).

From this in-vitro study, it can be demonstrated that there is an evolutionary pressure for cancer cells to activate pathways associated with signaling in stem cells, and at the same time, the scarcity of nutrients within a tumor mass causes the cell to be arrested in Go stage of the cell cycle, inducing nuclear reprogramming. The selection pressures lead to the rise of the cancer stem cells (Gurdon et al, 2003).

Citations

1)Tumor grade: Questions and Answers. National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Detection/tumor-grade

2) Baba Y, Yokota T, Spits H, Garrett KP, Hayashi S, Kincade PW. Constitutively active beta-catenin promotes expansion of multipotent hematopoietic progenitors in culture. J Immunol. 2006 Aug 15;177(4):2294-303

3) Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, Sundaresan T, Pastorino S, Park JK, Mikolaenko I, Maric D, Eberhart CG, Fine HA. Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res. 2005 Mar 15;65(6):2353-63.

4) Gurdon JB, Byrne JA, Simonsson S. Nuclear reprogramming and stem cell creation. Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11819-22.