RT Journal Article
SR Electronic
T1 Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 169615
DO 10.1101/169615
A1 Jacob G. Scott
A1 Andrew Dhawan
A1 Anita Hjelmeland
A1 Justin Lathia
A1 Masahiro Hitomi
A1 Alexander G. Fletcher
A1 Philip K. Maini
A1 Alexander R. A. Anderson
YR 2017
UL http://biorxiv.org/content/early/2017/07/28/169615.abstract
AB Since the first evidence for cancer stem cells in leukemia, experimentalists have sought to identify tumorigenic subpopulations in solid tumors. In parallel, scientists have argued over the implications of the existence of this subpopulation. On one side, the cancer stem cell hypothesis posits that a small subset of cells within a tumor are responsible for tumorigenesis and are capable of recapitulating the entire tumor on their own. Under this hypothesis, a tumor may be conceptualized as a series of coupled compartments, representing populations of progressively differentiated cell types, starting from stem cells. The allure of this model is that it elegantly explains our therapeutic failures: we have been targeting the wrong cells. Alternatively, the stochastic model states that all cells in a tumor can have stem-like properties, and have an equally small capability of forming a tumor. As tumors are, by nature, heterogeneous, there is ample evidence to support both hypotheses. We propose a mechanistic mathematical description that integrates these two theories, settling the dissonance between the schools of thought and providing a road map for integrating disparate experimental results into a single theoretical framework. We present experimental results from clonogenic assays that demonstrate the importance of defining this novel formulation, and the clarity that is provided when interpreting these results through the lens of this formulation.