The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell carcinoma

• Published in: Oral oncology Vol. 47; no. 11; pp. 1023 - 1031
• Main Authors: Yoon, Hye-Jung, Hong, Ji-Soo, Shin, Wui-Jung, Lee, Yoo-Jin, Hong, Kyoung-Ok, Lee, Jae-Il, Hong, Sam-Pyo, Hong, Seong-Doo
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.11.2011; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Western; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Case-Control Studies; Cell growth; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cripto-1; Epithelium - metabolism; Female; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Male; Medical sciences; Middle Aged; Migration; Mouth Mucosa - metabolism; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oral squamous cell carcinoma; Otolaryngology; Otorhinolaryngology. Stomatology; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Cell growth; Oral squamous cell carcinoma; Migration; Cripto-1; Cell proliferation; Cancerology; Stomatology; Oral cavity disease; ENT; Malignant tumor; Cancer
• ISSN: 1368-8375; 1879-0593; 1879-0593
• DOI: 10.1016/j.oraloncology.2011.07.019

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.