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Updated: Apr 25, 2026
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma
Oihana Murillo-Sauca1, Man Ki Chung2, June Ho Shin1
1Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA. Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA. .
Abstract:
Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.
Insights
CD271 specifically identifies tumor-initiating cells (TICs) in head and neck squamous cell carcinoma. Targeting CD271 inhibits cell cycle progression and tumor formation, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Cell Biology
- Cancer Stem Cell Research
Background:
- Tumor-initiating cells (TICs) drive cancer growth in head and neck squamous cell carcinoma (SCCHN).
- CD44 is a known marker for SCCHN TICs, but lacks functional activity for targeting.
- CD271, a marker for oral epithelial stem cells, was investigated for its role in SCCHN TICs.
Purpose of the Study:
- To investigate the expression and function of CD271 in SCCHN TICs.
- To determine if CD271 can serve as a functionally active target for SCCHN.
Main Methods:
- Flow cytometry to analyze CD271 expression on CD44+ SCCHN cells.
- Xenograft assays to assess tumor-initiating capacity of CD44+CD271+ cells.
- Functional assays involving CD271 inhibition and recombinant nerve growth factor (NGF) stimulation.
- Analysis of Erk phosphorylation pathways.
Main Results:
- CD271 expression is restricted to a subset of CD44+ SCCHN cells.
- The CD44+CD271+ subpopulation exhibits the highest tumorigenic potential.
- Loss of CD271 function causes G2-M cell cycle arrest and reduces tumor formation.
- CD271 activation by NGF enhances Erk phosphorylation; antibody blockade decreases Erk phosphorylation and tumor growth.
Conclusions:
- CD271 is a more specific marker for SCCHN TICs within the CD44+ population.
- CD271 is a functionally active receptor crucial for TIC proliferation and tumor initiation.
- CD271 represents a promising, targetable therapeutic molecule for SCCHN.
