title: Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma.
abstract: Background Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK) that is activated by fibrillar collagens. Although DDR2 contributes to the metastasis of some tumors, its role in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to investigate the expression level, clinical and pathological significance, and biologic function of DDR2 in HNSCC. Methods Real-time quantitative PCR, western blot, and immunohistochemical staining were employed to assess the expression levels of DDR2 in HNSCC specimens. Adenovirus-mediated overexpression of DDR2 was used to evaluate its consequences on cell proliferation, invasion, migration, and the process of hypoxia-induced epithelial-mesenchymal transition (EMT). Then nude mouse xenograft and tail vein metastasis models were utilized to validate the in vitro results. Results DDR2 was highly expressed in high grade HNSCC tissues and lowly expressed in low grade HNSCC tissues, but absent or rarely expressed in cancer-associated normal tissues. Both the frequency and expression intensity of DDR2 were significantly associated with tumor pathologic stage and lymph node metastasis. In vitro, DDR2 overexpression in HNSCC cells failed to alter cell proliferation but markedly accelerates cell invasion and migration as well as hypoxia-induced EMT. In vivo, elevated expression of DDR2 speeds up the metastasis of HNSCC cells to the lung. Conclusion DDR2 plays an important role in HNSCC metastasis, and might be a promising target for future therapies in this type of cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China; State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China; Department of Oral and Maxillofacial Surgery; Jinling Hospital; Clinical School of Medical College; Nanjing University; Nanjing, PR China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China; State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Oral and Maxillofacial Surgery; Jinling Hospital; Clinical School of Medical College; Nanjing University; Nanjing, PR China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Chuchao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; The Fourth Military Medical University; Xi'an, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Su
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D000070818:Discoidin Domain Receptors; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: DDR2; EMT; HNSCC; hypoxia; tumor metastasis