Colorectal cancer-initiating cells caught in the act

Abstract

Our increased awareness of the clonal organization of many hematological and solid cancers has dramatically changed our view on the design of novel therapeutic approaches for cancer. Tumor‐initiating cells (TIC) (a.k.a. cancer stem cells) are on the apex in this hierarchy and can self‐renew and differentiate, thereby continuously fueling tumor growth and metastasis formation. This process was previously thought to be unidirectional. Self‐renewing TIC therefore represent highly attractive targets for therapeutic intervention.

Figure 1. Utilizing lineage tracing, the Eduard Batlle (Cortina et al, 2017), Toshiro Sato (Shimokawa et al, 2017) and Frederic de Sauvage (Melo et al, 2017) groups demonstrate that LGR5⁺ cells are essential for tumor growth and metastasis formation of CRC

(A) Lineage tracing of primary human CRC‐derived organoid cells or murine organoid cells mimicking human CRC demonstrates tumor‐initiating cell (TIC) activity of LGR5⁺ cells in serial transplantation. (B) Induction of LGR5‐lineage tracing upon initial tumor formation demonstrates the existence of quiescent LGR5⁺ tumor cells (red arrows). (C) Following ablation of LGR5⁺ cells (purple) in established tumors in vivo, differentiated tumor cells (yellow) can re‐express LGR5 (red) and drive tumor re‐growth (blue). (D) Upon Lgr5⁺ ablation in transplantation models of metastasis formation, liver metastasis burden decreased, whereas primary tumor growth is not affected.