Elucidating the Role Played by Cancer Stem Cells in Cancer Growth

L. BARBERIS; L. BENÍTEZ; C.A. CONDAT

REVISTA DE MODELAMIENTO MATEMÁTICO DE SISTEMAS BIOLÓGICOS

Ediciones UTEM

Año: 2021

The cancer stem cell hypothesis states that cancer growth is propelled by a relatively small number of cancer stem cells (CSCs).These CSCs have been shown to play a crucial role in the growth and recurrence of many tumor types. The possibility that their eliminationbecomes an efficient cancer control procedure has even led to new therapeutic paradigms. On the other hand, from their early stages, mostsolid tumors grow in stressed environments. The stress field impacts on tumor evolution, and it is likely to affect different cancer cellpopulations in different ways. It is therefore of great interest to determine the nature and strength of the interactions between CSCs anddifferentiated tumor cells and how these interactions are affected by the mechanical properties of the environment. We have developed atwo-population mathematical model suitable to describe the initial stages of cancer growth and applied it to extract information from threedifferent experiments. Two of these experiments involve tumorspheres (spheroids resulting from the proliferation of a single CSC). In thesecases, the model validates the concept of CSC niche (the microenvironment responsible for signals that stimulate or inhibit CSC growth),shows that interspecific interactions stimulate growth, while intraspecific interactions are generally inhibitory, and indicates how substratehardness modifies growth. In the third experiment analyzed, where stress-induced growth suppression was measured in multicellular tumorspheroids, we were able to reconstruct the (unobserved) CSC fraction and found that medium rigidity eventually forces all cell interactionsto be competitive. We find that, under adverse environmental conditions the CSC fraction always remains nonzero. This lends support to thehypothesis of the existence of the niche as a regulatory maintenance mechanism whose understanding will be crucial to the development ofa successful therapy based on CSC elimination.