Distinct Types of Tumor-Initiating Cells Form Human Colon Cancer Tumors and Metastases
Distinct Types of Tumor-Initiating Cells Form Human Colon Cancer Tumors and Metastases
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DOI：
10.1016/j.stem.2011.08.010
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发表时间：
2011-10-07
期刊：
影响因子：
23.9
通讯作者：
Glimm, Hanno
中科院分区：
文献类型：
--
作者：
Dieter, Sebastian M.;Ball, Claudia R.;Glimm, Hanno
人结肠癌含有一小部分肿瘤起始细胞（TIC），被认为是一个功能同质的干细胞样群体，驱动肿瘤维持和转移形成。我们发现了意想不到的细胞内的TIC区室，其中包含三种类型的TIC的异质性。广泛自我更新的长期TIC（LT-TIC）在连续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）仅在原代小鼠中促成肿瘤形成。罕见的延迟贡献型TIC（DC-TIC）仅在二级或三级小鼠中活跃。骨髓被认为是LT-TIC的重要储存库。转移形成几乎完全由自我更新的LT-TIC驱动。我们的研究结果表明，肿瘤的启动，自我更新，转移的形成是有限的，在原发性人类结肠癌的TIC的特定亚群。我们将LT-TIC确定为旨在根除自我更新致瘤性和转移性结肠癌细胞的治疗的可量化靶点。
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.