Today, we have no doubts that cancer stem cells (CSC) possess great heterogeneity. So far, genotypic and phenotypic CSC heterogeneity was unveiled. We think, that despite some differences in genotype, phenotype and signaling, CSC have the same tumorigenic potential in vivo. Now, we got the first evidence for functional heterogeneity of CSC. The study from Dieter at al. demonstrates the functional difference between colon CSC subsets.
It was proposed that metastatic cells could be an equivalent of CSC from primary tumor. Dieter at al. have created clonal tracking system, which allowed to identify distinct functional subsets of colon tumor-initiating cells (TICs):
- extensively self-renewing long-term TICs (LT-TICs) – tumorigenicity in serial xenotransplants, exclusive metastatic potential;
- transient amplifying cells (T-TACs) – tumorigenicity only in primary mice (limited self-renewal);
- delayed contributing TICs (DC-TICs) – very rare, exclusively tumorigenic in 2nd and 3rd xenotransplans.
Because only LT-TICs and DC-TICs were able to self-renew, the authors called them cancer stem cells. Interestingly, these two CSC subsets could be responsible for different events in tumor progression – metastases and dormancy:
Bone marrow was identified as an important reservoir of LT-TICs. Metastasis formation was almost exclusively driven by self-renewing LT-TICs. Our results demonstrate that tumor initiation, self-renewal, and metastasis formation are limited to particular subpopulations of TICs in primary human colon cancer.
Graphical representation of Dieter et al. findings:
Full text is available in open access.