title: Insulin-like growth factor-II mRNA binding protein-3 and podoplanin expression are associated with bone invasion and prognosis in oral squamous cell carcinoma.
abstract: OBJECTIVE
  This study aimed to evaluate the prognostic implications of insulin-like growth factor-II mRNA binding protein-3 (IMP3) and podoplanin (PDPN) as therapeutic targets against oral squamous cell carcinoma (OSCC) with bone invasion.
  
  
  METHODS
  We elucidated the correlation of IMP3 and PDPN expression with bone invasion in 160 OSCC tissue specimens, and assessed a mouse calvarium xenograft model using an IMP3- and PDPN-depleted OSCC cell line.
  
  
  RESULTS
  The retrospective analysis revealed that the expression of IMP3 and PDPN is significantly correlated with T stage, lymph node metastasis, and the overall survival of OSCC patients. In addition, the dual expression of IMP3 and PDPN but not the single expression of either IMP3 or PDPN was associated with bone invasion and the number of osteoclasts in patients with OSCC. In support of these findings, IMP3 or PDPN depletion inhibited the invasive capacity of OSCC cells in a three-dimensional culture system, tumorigenesis, and regional bone destruction in a xenograft mouse model. In addition, IMP3 or PDPN depletion inhibited the expression of interleukin (IL)-6 and IL-8 in OSCC cells, and decreased the expression of receptor activator of NF-κB ligand (RANKL) in xenograft tumor tissues of OSCC.
  
  
  CONCLUSIONS
  These results suggest that IMP3 and PDPN may have strong influence on the pathogenesis of OSCC, especially in bone invasion, and may serve as novel therapeutic targets with prognostic implications for bone-invasive OSCC.
authors.affiliation: Department of Dental Hygiene, College of Health Science, Eulji University, Seoul, Korea.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Department of Oral Pathology, Graduate School, Yonsei University College of Dentistry, Seoul, Korea; Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Ahn
authors.affiliation: Department of Oral Pathology, Graduate School, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Sook
authors.initials: S
authors.lastname: Moon
authors.affiliation: Department of Dermatology, Yanbian University Hospital, Yanji City, Jilin province, China.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Cha
authors.affiliation: Department of Oral Pathology, Graduate School, Yonsei University College of Dentistry, Seoul, Korea; Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yanbian University Hospital, Yanji City, Jilin province, China; Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea. Electronic address: zhangxianglan@yuhs.ac.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D011379:Prognosis; D053245:RANK Ligand / Q000096:biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis / Q000187:drug effects; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D000098853:Podoplanin
chemical_list: D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D053246:Receptor Activator of Nuclear Factor-kappa B; C498780:IGF2BP3 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C505689:Tnfsf11 protein, mouse
keywords: Bone invasion; IMP3; Oral squamous cell carcinoma; PDPN