Title | Basal stem cells contribute to squamous cell carcinomas in the oral cavity. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Tang X-H, Scognamiglio T, Gudas LJ |
Journal | Carcinogenesis |
Volume | 34 |
Issue | 5 |
Pagination | 1158-64 |
Date Published | 2013 May |
ISSN | 1460-2180 |
Keywords | 4-Nitroquinoline-1-oxide, Animals, Carcinogens, Carcinoma, Squamous Cell, Cell Proliferation, Epithelium, Lac Operon, Mice, Mice, Transgenic, Mouth, Mouth Neoplasms, Quinolones, Stem Cells, Tongue Neoplasms |
Abstract | The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell lineage tracing approach (adult K14-CreER(TAM); ROSA26 mice transiently treated with tamoxifen) to identify and track normal epithelial stem cells (SCs) in mouse tongues by X-gal staining and to determine if these cells become neoplastically transformed by treatment with a carcinogen, 4-nitroquinoline 1-oxide (4-NQO). Here, we show that in normal tongue epithelia, X-gal(+) cells formed thin columns throughout the entire epithelium 12 weeks after tamoxifen treatment, indicating that the basal layer contains long-lived SCs that produce progeny by asymmetric division to maintain homeostasis. Carcinogen treatment results in a ~10-fold reduction in the total number of X-gal(+) clonal cell populations and horizontal expansion of X-gal(+) clonal cell columns, a pattern consistent with symmetric division of some SCs. Finally, X-gal(+) SCs are present in papillomas and invasive OCSCCs, and these long-lived X-gal(+) SCs are the cells of origin of these tumors. Moreover, the resulting 4-NQO-induced tumors are multiclonal. These findings provide insights into the identity of the initiating cells of oral cancer. |
DOI | 10.1093/carcin/bgt021 |
Alternate Journal | Carcinogenesis |
PubMed ID | 23358851 |
Grant List | 5T32 CA062948 / CA / NCI NIH HHS / United States R01DE10389 / DE / NIDCR NIH HHS / United States |
Related Faculty:
Theresa Scognamiglio, M.D.