Abstract
We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. Although many Bmi1-positive cells within the tongue cancer specimens failed to proliferate, some proliferated continuously and supplied tumor cells to the surrounding area. This process eventually led to the formation of areas derived from single cells after 1–3 months, as determined using the multicolor lineage tracing method, indicating that such cells could serve as cancer stem cells. These results indicate that LESCs could serve as the origin for tongue cancer and that cancer stem cells are present in tongue tumors.
Highlights
We recently found that in the normal lingual epithelium, long-term stem cells are located in the interpapillary pit (IPP)[11]
Carcinoma in situ or invasive SSC was composed of several cell clusters, each of which was derived from a different clone
By labeling Bmi1+ cells in Bmi1creER/+/Rosa26rbw/+ mice prior to inducing carcinogenesis, we examined whether tongue cancer originated from Bmi1+ LESCs
Summary
4-NQO induction of tongue cancer in C57BL/6, Bmi1creER/+/Rosa26rbw/+ mice, and Rosa26CreERT2/rbw mice. To determine if the origin of 4-NQO-induced tongue tumors is monoclonal, we labeled all epithelial cells with random colors and followed their fates in Rosa26CreERT2/rbw mice[14,15,16]. To determine the number of such cell clusters present in tongue tumors and to examine the clonal origin of these tumors, we labeled all cells of the tongue before inducing carcinogenesis by 4-NQO (Supplementary Fig. 2a).
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