Distinct Types of Tumor-Initiating Cells Form Human Colon Cancer Tumors and Metastases

被引：257

作者：

Dieter, Sebastian M. ^{[1
,2
]}

Ball, Claudia R. ^{[1
,2
]}

Hoffmann, Christopher M. ^{[1
,2
]}

Nowrouzi, Ali ^{[1
,2
]}

Herbst, Friederike ^{[1
,2
]}

Zavidij, Oksana ^{[1
,2
]}

Abel, Ulrich ^{[1
,2
,5
]}

Arens, Anne ^{[1
,2
]}

Weichert, Wilko ^{[3
]}

Brand, Karsten ^{[3
]}

Koch, Moritz ^{[4
]}

Weitz, Juergen ^{[4
]}

Schmidt, Manfred ^{[1
,2
]}

von Kalle, Christof ^{[1
,2
]}

Glimm, Hanno ^{[1
,2
]}

机构：

[1] Natl Ctr Tumor Dis NCT, Dept Translat Oncol, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, Dept Surg, D-69120 Heidelberg, Germany

[5] Heidelberg Univ, Dept Med Biometry, D-69120 Heidelberg, Germany

来源：

CELL STEM CELL | 2011年 / 9卷 / 04期

关键词：

INTESTINAL STEM-CELL; GENE-THERAPY; COLORECTAL-CANCER; PANCREATIC-CANCER; PHENOTYPIC CHARACTERIZATION; PROGNOSTIC-SIGNIFICANCE; REPOPULATING ACTIVITY; MELANOMA-CELLS; BONE-MARROW; VECTOR;

D O I：

10.1016/j.stem.2011.08.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：357 / 365

页数：9

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