Hemophagocytosis‐mediated keratinization in oral carcinoma in situ and squamous cell carcinoma: A possible histopathogenesis of keratin pearls

  • Kamal Al‐Eryani
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Jun Cheng
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Tatsuya Abé
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Manabu Yamazaki
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Satoshi Maruyama
    Oral Pathology Section, Department of Surgical Pathology Niigata University Hospital Niigata Japan
  • Masayuki Tsuneki
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Ahmed Essa
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Hamzah Babkair
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
  • Takashi Saku
    Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

書誌事項

公開日
2013-06-20
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/jcp.24364
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Although the histopathogenetic process of keratin pearls is still poorly understood, acceleration of keratinization in squamous cell carcinoma (SCC) cells may represent one possible therapeutic avenue. Based on our histopathological observations, we have hypothesized that SCC cells are keratinized by phagocytosis of extravasated erythrocytes. To confirm this hypothesis, we firstly examined immature keratin pearls in oral carcinoma in situ (CIS) and mature ones in SCC by immunohistochemistry. Concentric dyskeratotic cells in CIS keratin pearls became positive for keratin (K) 10, K17, heme oxygenase‐1 (HO‐1), or protease activated receptor‐2 (PAR‐2), a candidate regulator for hemophagocytosis. When ZK‐1 cells, an SCC cell system, were incubated with human peripheral blood erythrocytes, or with crude and purified hemoglobins (Hbs), their erythro‐hemophagocytotic activities were confirmed by immunofluorescence. Immunofluorescence signals for K10, K17, and HO‐1 were enhanced due to hemophagocytosis in time‐dependent manners. mRNA expression levels for the three molecules were most enhanced by purified Hb, followed by crude Hb and erythrocytes. K17/K10 mRNA expression levels were more elevated when PAR‐2 was activated in ZK‐1 cells. The results indicated that immature and mature keratin pearls in CIS and SCC were generated by oxidative stresses derived from erythro‐hemophagocytosis, which might mediate HO‐1 expression and be regulated by PAR‐2. Thus, hemorrhage from the rupture of blood vessels can be one of the triggers for keratin pearl formation in oral CIS and SCC. J. Cell. Physiol. 228: 1977–1988, 2013. © 2013 Wiley Periodicals, Inc.</jats:p></jats:sec>

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