Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Cell Stem Cell. 2011 Oct 4;9(4):357-65. doi: 10.1016/j.stem.2011.08.010.
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.
人类结肠癌中存在一小部分肿瘤起始细胞（TICs），它们被认为是一种功能上同质的干细胞样群体，驱动肿瘤的维持和转移形成。我们在 TIC 区发现了出乎意料的细胞异质性，其中包含三种类型的 TICs。具有广泛自我更新能力的长期 TICs（LT-TICs）在连续的异种移植中维持肿瘤形成。具有有限或无自我更新能力的肿瘤瞬时扩增细胞（T-TACs）仅在原发性小鼠中有助于肿瘤形成。罕见的迟发性贡献 TICs（DC-TICs）仅在继发性或三级小鼠中活跃。骨髓被确定为 LT-TICs 的重要储存库。转移形成几乎完全由自我更新的 LT-TICs 驱动。我们的研究结果表明，肿瘤起始、自我更新和转移形成仅限于原发性人结肠癌中特定的 TIC 亚群。我们将 LT-TICs 鉴定为针对消除自我更新的致瘤和转移性结肠癌细胞的治疗的可量化靶标。
