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

Cell Stem Cell. 2011 Oct 4;9(4):357-65. doi: 10.1016/j.stem.2011.08.010.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Bone Marrow / pathology
  • Cell Proliferation
  • Colonic Neoplasms / pathology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / classification
  • Neoplastic Stem Cells / pathology*
  • Spheroids, Cellular / pathology
  • Time Factors
  • Tumor Cells, Cultured