title: 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.
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Atsumi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Department of Urology and Andrology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komai
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Omachi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Kiyomichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishigaki
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Saiga
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.|Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ohsugi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tokuyama
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imahashi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hisha
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.affiliation: Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueno
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014059:Tongue / Q000378:metabolism; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000378:metabolism*
chemical_list: C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D015112:4-Nitroquinoline-1-oxide; D063150:Polycomb Repressive Complex 1