1. Possible sources of tumor cells of origin.
Possible sources of tumor cells of origin. (A) The canonical multi-hit model of tumorigenesis posits that stem cells (SCs) accumulate and store the necessary mutations for tumors to initiate. The tumor would arise from the normal SC niche and would not necessitate plasticity at any point to occur. (B) Experiments in many tissues have demonstrated that SCs can be replaced by more differentiated cells that revert to SCs and re-enter the niche. This allows for mutations needed for tumor initiation to be acquired and stored while the cell is in a non-SC fate (i.e. label-retaining cell, committed progenitor, differentiated cell, etc.). This would appear as tumors arising from the normal SC niche, yet would still incorporate earlier plasticity only visible through careful tracking. (C) Tumors may also arise from non-SC populations which never fully revert to a SC fate and re-enter the niche. Tumors arising directly from mature cells would originate in a tissue area outside of the normal SC niche.
Joseph Burclaff, and Jason C. Mills Dis. Model. Mech. 2018;11:dmm035071
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