Biomedical Engineering Reference
In-Depth Information
While it has been shown that different oncogenic stresses on pCSCs can give
rise to tumors of varying malignancy, it is still unclear how these cells are
derived. pCSCs could be adult stem cells that acquire cancerous mutations.
Alternatively pCSCs may arise frommore committed progenitor cells that have
regained self-renewal properties along with cancerous phenotypes. These two
possibilities are illustrated in Fig. 1. Similar challenges presented to normal
stem cells versus their more committed progenitors could result in varying levels
of malignancy stemming from the inherent characteristics of the originally
targeted cells. Transforming events appear to require the capability of replica-
tion which is limited to less-differentiated stem and progenitor cells thereby
excluding mature somatic cells as likely CSC precursors. While current prevail-
ing thought favors these more pluripotent cells in formation of CSCs, evidence
of cellular plasticity exists that blurs the canonical hierarchy of stem cells and
raises questions regarding CSC origins. Terminally differentiated fibroblasts,
Fig. 1 Models of different CSC origin giving rise to tumors of varying metastatic potential. In
normal adult tissues, normal stem cells give rise to more committed progenitor cells which in
turn give rise to terminally differentiated cells (central panel). Cancer stem cells could arise via
oncogenic transformation of either the stem cell population or the progenitor population.
Tumors derived from these different precursors and/or with different oncogenic events could
show varying malignancy and metastatic potential. Different cellular origin could also explain
heterogeneity observed within or amongst tumors. There are speculations that adult stem cells
would form the most metastatic lesions owing to their enhanced proliferative capabilities and
pluripotency
