کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2077728 | 1079740 | 2011 | 9 صفحه PDF | دانلود رایگان |
SummaryHuman 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.
Graphical AbstractFigure optionsDownload high-quality image (328 K)Download as PowerPoint slideHighlights
► Human colon cancer contains distinct classes of tumor-initiating cells
► Self-renewal is limited to long-term TICs but not tumor transient amplifying cells
► Metastasis formation is exclusively driven by long-term TICs
► TICs home to and persist in the bone marrow
Journal: - Volume 9, Issue 4, 4 October 2011, Pages 357–365