Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer

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.

Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma

“…This chemical is used to generate an oral cancer model in mice and rats. 4-NQO is administered either locally on the tongue or adding 4NQO to the drinking water [165,166,167]. Long-term administration of 4-NQO leads to a progression of carcinogenesis and includes hyperplasia, dysplasia, preneoplastic as well as neoplastic lesions.…”

HPV+ve/−ve oral-tongue cancer stem cells: A potential target for relapse-free therapy

“…Further, specific targeting and pharmacological inhibition of BMI-1 can inhibit tumor sphere formation and reduced tumorigenesis in TSCC [ 47 , [112] , [113] , [114] ]. Toshihiro Tanaka and co-workers (2016) used multicolor lineage tracing method and revealed that BMI1-positive tumorigenic cells display TCSC-like characteristics in a chemically induced tongue cancer mouse model [115] . Further, inhibition of BMI-1 through PTC-209, PTC596 inhibitors reduced BMI-1 expression, tumorsphere formation, the percentage of ALDH1 +ve subpopulation and increased chemosensitivity against 5-FU and cisplatin in TSCC cells ( Table 2 ) [ 51 , 112 , 114 , 116 ].…”

“…Altered expression of BMI-1 has been found to be correlated with self-renewal of CSC in HNC [ 47 , 140 ]. BMI-1 +ve CSCs in TSCC cells have been associated with drug resistance in a mouse model [ 115 , 141 ]. Recently, Chen and co-workers (2017) investigated that BMI-1 +ve CSCs can mediate invasive growth and lymph node metastasis in a mouse model and the primary oral tumors associated with high tumorigenicity, invasiveness and cisplatin-resistance leading to overexpression of transcription factor activator protein-1 (AP-1) [142] .…”

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

“…Consistently, BMI1 overexpression is highly correlated with malignant phenotypes and thereby causes malignant transformation in HCC [ 219 , 220 , 221 ]. Aberrant BMI1 expression contributes to the maintenance of CSC subpopulations in multiple types of cancer [ 34 , 222 , 223 , 224 ]. Additionally, BMI1 is involved in the maintenance of the tumorigenic SP subpopulation in liver cancer [ 113 ].…”