A defining property of stem cells is their ability to undergo asymmetric division, resulting in both a self renewing population of stem cells and a more differentiated non-stem cell population.
In contrast, in the bulk of more differentiated non-neurosphere GBM cells and in GBM surgical specimens, NEU4 expression is very low.
The concept that cancer develops in a hierarchical tree from disease-originating cancer stem cells (CSCs) that self-renew and give rise to more differentiated, non-cancer-initiating cells by asymmetric division was first documented in leukemia two decades ago.
The data on plasmablasts in murine and human lupus provide evidence that these cells are susceptible to anti-proliferative immunosuppressive agents, whereas more differentiated non-dividing plasma cells show resistance to these drugs [ 23].
In the CSC-enriched fraction isolated from several PDX models we found that the cell cycle regulators p21 and p57 were consistently upregulated and Cyclin D1 downregulated, as compared with the more differentiated non-CSC progenies, at RNA and protein levels (figure 2A,B).
Furthermore, consistent with a stem cell model is the observation that tumor stem cells are able to be serially passaged in NOD/SCID mice, each time generating a stem cell population, as well as the more differentiated non-tumorigenic cells forming the bulk of the tumor [ 27].
These cells grow rapidly at 33°C (permissive), but adopt a more differentiated state at 39°C (non-permissive).
Phenotype switching between the cancer stem-cell state, here XHigh (where X can be one of the stem-cell markers, such as CD117, MDR1, CD44, ALDH1; Hanahan and Weinberg, 2011; Medema, 2013), and the more differentiated, here XLow, state epitomises non-genetic plasticity of cancer cells.
Recently, a positive correlation between IRS-1 nuclear expression and a more well-differentiated, non-metastatic phenotype for ductal breast cancer was reported [ 46].
Just as dermal fillers have become more differentiated to increase their longevity, the non-injectible long-lasting implants are becoming more developed to mimic accurate viscoelastic properties of the facial soft tissues.
In contrast, more differentiated primary tumor cells are less or completely non-tumorigenic in immunocompromised mice [1], [2].
