title: Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia.
abstract: Oral squamous cell carcinomas (SCCs) are frequently associated with pre-invasive lesions including carcinoma in-situ (CIS), and CISs further form lateral interfaces against surrounding normal or dysplastic epithelia (ND). At the interface where keratin (K) 17 positive (+) SCC/CIS cells are in contact with K13+ ND cells, "cell competition" must be evoked between two such different cell types. Thus, the aim of this study was to characterize the histopathology of the SCC/CIS-ND interface and to determine protein profiles around the interface by proteomics. A total of 112 lateral interfaces were collected from 55 CIS and 57 SCC foci, and they were investigated by immunohistochemistry and liquid chromatography-tandem mass spectrometry. The interfaces were morphologically classified into three types: vertical, oblique, and convex. There were several cellular changes characteristic to the interface, including apoptosis and hyaline bodies, which were more emphasized in SCC/CIS sides. The results suggested that ND cells were winners of cell competition against SCC/CIS cells. Then, the interfaces were divided into four vertical segments, and each segment was separately laser-microdissected from tissue sections with immunostaining for K13 or K17; the four segments included SCC/CIS away from (#1) or adjacent to (#2) the interface, and ND adjacent to (#3) or away from (#4) the interface. Proteome analyses revealed approximately 4000 proteins from SCC/CIS sides [#1 and #2] and 2800 proteins from ND sides [#3 and #4]. We quantitatively selected the top 25 proteins including ladinin-1 or interleukin-1 receptor antagonist protein, which were most contrastively increased or decreased in SCC/CIS or ND sides, respectively, and their specific immunohistochemical expression modes were confirmed in tissue sections as well as in cultured SCC cells. These molecules should be involved in the cellular crosstalk toward cell competition at the lateral interface of oral SCC/CIS and would be new candidates for histopathological distinction of oral malignancies.
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan. Electronic address: t-abe@dent.niigata-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abé
authors.affiliation: Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Biofluid Biomarker Center (BB-C), Institute for Research Collaboration and Promotion, Niigata University, Niigata, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hamzah
authors.initials: H
authors.lastname: Babkair
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sumita
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Biofluid Biomarker Center (BB-C), Institute for Research Collaboration and Promotion, Niigata University, Niigata, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan; Osaka Dental University, Hirakata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009061:Mouth Mucosa / Q000473:pathology; D040901:Proteomics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
keywords: Carcinoma in-situ; Interface; Keratin 13/17; Lateral invasion front; Proteomics; Squamous cell carcinoma