Periostin Promotes Invasiveness and Metastasis of Oral Cancer via Epithelial-mesenchymal Transition

被引:0
作者
Won, Seongjun [1 ,2 ,3 ]
Hah, Young-Sool [3 ,4 ]
Cheon, So Young [4 ]
Yim, Chae Dong [1 ,2 ,3 ]
Park, Sang-Wook [1 ,2 ,3 ]
Lee, Seung-Jun [5 ]
Seo, Ji Hyun [3 ,6 ]
Park, Jung Je [1 ,2 ,3 ,4 ]
机构
[1] Gyeongsang Natl Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Jinju, South Korea
[2] Gyeongsang Natl Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Jinju, South Korea
[3] Gyeongsang Natl Univ, Inst Med Sci, Jinju, South Korea
[4] Gyeongsang Natl Univ Hosp, Biomed Res Inst, Jinju, South Korea
[5] Gyeongsang Natl Univ, Dept Convergence Med Sci, Jinju, South Korea
[6] Gyeongsang Natl Univ, Coll Med, Dept Pediat, Jinju, South Korea
基金
新加坡国家研究基金会;
关键词
Periostin; oral squamous cell carcinoma (OSCC); epithelial-mesenchymal transition (EMT); invasiveness and metastasis; prognostic marker; EXTRACELLULAR-MATRIX; TUMOR ANGIOGENESIS; POOR-PROGNOSIS; GASTRIC-CANCER; INVASION; GROWTH; CELLS; RADIORESISTANCE; EXPRESSION; PROTEIN;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: Oral squamous cell carcinoma (OSCC) is a significant global health burden, with a modest 5-year survival rate; therefore, novel therapeutic targets are needed. Periostin, an extracellular matrix protein, is implicated in tumor progression, yet its role in OSCC, particularly via epithelial-mesenchymal transition (EMT), is poorly understood. Materials and Methods: We investigated periostin's role in OSCC using a multifaceted approach: retrospective analysis of 97 OSCC patient samples, bioinformatics analyses of GEO and TCGA datasets, and in vitro/in vivo experiments using the HNSCC-31 cell line and xenograft mouse models. Periostin expression was assessed via immunohistochemistry and western blotting. Functional effects were evaluated through cell viability, colony formation, migration, invasion, and EMT marker expression assays following periostin over-expression (Ad-POSTN), knockdown (Lenti-shPOSTN) or recombinant periostin treatment. Results: Periostin expression was significantly elevated in OSCC tissue compared than normal tissue (p<0.001) and correlated with lymph node metastasis (p=0.011), higher AJCC stage (p=0.008), and recurrence (p=0.001). High periostin levels independently predicted poor disease-free [hazard ratio (HR)=2.329, p=0.019] and overall survival (HR=2.842, p=0.009). In vitro, periostin up-regulation enhancedviability, colony formation, migration, and invasion, and EMT (increased vimentin, Snail, MMP-9, N-cadherin; decreased E-cadherin), while knockdown reversed these effects. In vivo, Ad-POSTN xenografts were significantly larger (p<0.05) and heavier (p<0.05) and showed increased periostin expression histologically. Conclusion: Periostin promotes OSCC progression by enhancing invasiveness and metastasis via EMT. It represents a potential prognostic marker and therapeutic target. These findings highlight the need for further clinical validation of periostin-targeted therapies for management of OSCC.
引用
收藏
页码:3099 / 3115
页数:17
相关论文
共 41 条
[1]   Incidence of Oral Cancer Occult Metastasis and Survival of T1-T2N0 Oral Cancer Patients [J].
Abu El-Naaj, Imad ;
Leiser, Yoav ;
Shveis, Myrela ;
Sabo, Edmond ;
Peled, Micha .
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2011, 69 (10) :2674-2679
[2]  
Anderson NM, 2020, CURR BIOL, V30, pR921, DOI 10.1016/j.cub.2020.06.081
[3]   EMT: 2016 [J].
Angela Nieto, M. ;
Huang, Ruby Yun-Ju ;
Jackson, Rebecca A. ;
Thiery, Jean Paul .
CELL, 2016, 166 (01) :21-45
[4]   Periostin inhibits hypoxia-induced apoptosis in human periodontal ligament cells via TGF-β signaling [J].
Aukkarasongsup, Paveenarat ;
Haruyama, Naoto ;
Matsumoto, Tsutomu ;
Shiga, Momotoshi ;
Moriyama, Keiji .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 441 (01) :126-132
[5]   Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death:: role of the β4 integrin and the PI3k pathway [J].
Baril, P. ;
Gangeswaran, R. ;
Mahon, P. C. ;
Caulee, K. ;
Kocher, H. M. ;
Harada, T. ;
Zhu, M. ;
Kalthoff, H. ;
Crnogorac-Jurcevic, T. ;
Lemoine, N. R. .
ONCOGENE, 2007, 26 (14) :2082-2094
[6]   Periostin, a matrix specific protein, is associated with proliferation and invasion of pancreatic cancer [J].
Ben, Qi-Wen ;
Jin, Xiao-Long ;
Liu, Jun ;
Cai, Xia ;
Yuan, Fei ;
Yuan, Yao-Zong .
ONCOLOGY REPORTS, 2011, 25 (03) :709-716
[7]   Expression of Periostin in Mammary Cancer Cells of Female Dogs [J].
Borecka, Paulina ;
Ciaputa, Rafal ;
Janus, Izabela ;
Bubak, Joanna ;
Piotrowska, Aleksandra ;
Ratajczak-Wielgomas, Katarzyna ;
Podhorska-OkolOw, Marzenna ;
Dziegiel, Piotr ;
Nowak, Marcin .
IN VIVO, 2020, 34 (06) :3255-3262
[8]   Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].
Bray, Freddie ;
Laversanne, Mathieu ;
Sung, Hyuna ;
Ferlay, Jacques ;
Siegel, Rebecca L. ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2024, 74 (03) :229-263
[9]   Overexpression of Periostin in Tumor Biopsy Samples Is Associated With Prostate Cancer Phenotype and Clinical Outcome [J].
Cattrini, Carlo ;
Rubagotti, Alessandra ;
Nuzzo, Pier Vitale ;
Zinoli, Linda ;
Salvi, Sandra ;
Boccardo, Simona ;
Perachino, Marta ;
Cerbone, Luigi ;
Vallome, Giacomo ;
Latocca, Maria Maddalena ;
Zanardi, Elisa ;
Boccardo, Francesco .
CLINICAL GENITOURINARY CANCER, 2018, 16 (06) :E1257-E1265
[10]   Socioeconomic inequalities and oral cancer risk: A systematic review and meta-analysis of case-control studies [J].
Conway, David I. ;
Petticrew, Mark ;
Marlborough, Helen ;
Bertbiller, Julien ;
Hashibe, Mia ;
Macpherson, Lorna M. D. .
INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (12) :2811-2819