title: Sprouty2 protein is downregulated in human squamous cell carcinoma of the head and neck and suppresses cell proliferation in vitro.
abstract: Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.
authors.affiliation: Department of Hematology and Oncology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
authors.forename: Chiang-Liang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Dentology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
authors.forename: Wei-Fan
authors.initials: WF
authors.lastname: Chiang
authors.affiliation: Department of Hematology and Oncology, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C.
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Tung
authors.affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan, R.O.C.
authors.forename: Jeng-Long
authors.initials: JL
authors.lastname: Hsieh
authors.affiliation: Department of Otolaryngology, National Cheng Kung University Hospital, Tainan 70101, Taiwan, R.O.C.
authors.forename: Jenn-Ren
authors.initials: JR
authors.lastname: Hsiao
authors.affiliation: Department of Hematology and Oncology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Huang
authors.affiliation: National Kaohsiung University of Hospitality and Tourism, Kaohsiung 81271, Taiwan, R.O.C.
authors.forename: Li-Yia
authors.initials: LY
authors.lastname: Feng
authors.affiliation: Department of Dentology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Dentistry, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C.
authors.forename: Shyun-Yeu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Hematology and Oncology, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Tsao
authors.affiliation: Department of Hematology and Oncology, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C.
authors.forename: Yin-Hsun
authors.initials: YH
authors.lastname: Feng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077157:Sorafenib; D000077195:Squamous Cell Carcinoma of Head and Neck; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C485561:SPRY2 protein, human; D009536:Niacinamide; D000077157:Sorafenib; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase