title: Distinct types of tumor-initiating cells form human colon cancer tumors and metastases.
abstract: 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.
authors: Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Sebastian M
authors: SM
authors: Dieter
authors: Claudia R
authors: CR
authors: Ball
authors: Christopher M
authors: CM
authors: Hoffmann
authors: Ali
authors: A
authors: Nowrouzi
authors: Friederike
authors: F
authors: Herbst
authors: Oksana
authors: O
authors: Zavidij
authors: Ulrich
authors: U
authors: Abel
authors: Anne
authors: A
authors: Arens
authors: Wilko
authors: W
authors: Weichert
authors: Karsten
authors: K
authors: Brand
authors: Moritz
authors: M
authors: Koch
authors: Jürgen
authors: J
authors: Weitz
authors: Manfred
authors: M
authors: Schmidt
authors: Christof
authors: C
authors: von Kalle
authors: Hanno
authors: H
authors: Glimm
mesh_terms: D000368:Aged; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000145:classification / Q000473:pathology*; D018874:Spheroids, Cellular / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured