title: Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis.
abstract: Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two proto-oncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P=0.67), whereas HMGA2 expression was associated with decreased overall survival (P=0.05). Quantitative real-time reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells.
authors.affiliation: Department of Oral Surgery, School of Medicine, Tokai University, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Masaki
authors.initials: M
authors.lastname: Yazawa
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsumoto
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshimoto
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ota
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kaneko
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D063150:Polycomb Repressive Complex 1