title: The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell carcinoma.
abstract: Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, remains a lethal disease in over 50% of cases diagnosed annually, due mostly to late detection of this cancer in its advanced stages despite the easy accessibility of the oral cavity for regular examinations. Cripto-1 is a member of the epidermal growth factor (EGF)-CFC protein family and is involved in the activation of several different signaling pathways during embryonic development and cellular transformation. Although the Cripto-1 protein is overexpressed in several human cancers including breast, colon, cervix, gastric, and pancreatic cancer, no prior study has evaluated Cripto-1 expression in OSCC. Therefore, our aims in this study were to examine Cripto-1 expression in clinical samples of OSCC patients using immunohistochemistry, to analyze the correlation between Cripto-1 expression and clinicopathologic parameters, and to identify the oncogenic roles of Cripto-1 in OSCC cell lines. Both epithelial dysplasia (73.3%) and OSCC (55.5%) tissue samples showed significantly higher expression of Cripto-1 than normal mucosa (20%) (p=0.031). In the OSCC samples, there was a significant correlation between Cripto-1 expression and the histological differentiation of OSCC (p=0.015) and a high PCNA index (p=0.011). The in vitro cell proliferation assays demonstrated that recombinant human Cripto-1 (rhCripto-1) induced both SCC-4 and SCC-25 cells to proliferate as compared with control cells (p<0.05 and p<0.01, respectively). In in vitro migration assays, treatment of SCC-4 and SCC-25 cells with rhCripto-1 protein induced a 2.4-fold and 1.7-fold-increase in cell migration, respectively (p=0.000 and p=0.008, respectively). Taken together, our data suggest that Cripto-1 plays a role in the malignant transformation of the oral mucosa and is involved in the tumorigenesis and progression of OSCC by promoting the growth and migration of malignant cells.
authors.affiliation: Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 28 Yeongeon-dong, Chongno-gu, Seoul 110-749, Republic of Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Ji-Soo
authors.initials: JS
authors.lastname: Hong
authors.forename: Wui-Jung
authors.initials: WJ
authors.lastname: Shin
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kyoung-Ok
authors.initials: KO
authors.lastname: Hong
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Sam-Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Seong-Doo
authors.initials: SD
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human