期刊
CARCINOGENESIS
卷 34, 期 5, 页码 1158-1164出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgt021
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资金
- National Institutes of Health [R01DE10389]
- WCMC funds
- National Cancer Institute [5T32 CA062948]
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.
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