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Dieter, S.M.* ; Ball, C.R.* ; Hoffmann, C.M.* ; Nowrouzi, A.* ; Herbst, F.* ; Zavidij, O.* ; Abel, U.* ; Arens, A.* ; Weichert, W.* ; Brand, K.* ; Koch, M.* ; Weitz, J.* ; Schmidt, M.* ; von Kalle, C.* ; Glimm, H.*

Distinct types of tumor-initiating cells form human colon cancer tumors and metastases.

Cell Stem Cell 9, 357-365 (2011)

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Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term TICs (LT-TICs) maintained tumor formation in serial xenotransplants. Tumor transient amplifying cells (T-TACs) with limited or no self-renewal capacity contributed to tumor formation only in primary mice. Rare delayed contributing TICs (DC-TICs) were exclusively active in secondary or tertiary mice. 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. We identify LT-TICs as a quantifiable target for therapies aimed toward eradication of self-renewing tumorigenic and metastatic colon cancer cells.

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