title: Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is one of the most drug-refractory cancers. The aim of this study is to discover a novel therapeutic target molecule for clear cell RCC (CCRCC), which accounts for the majority of RCC.
  
  
  METHODS
  Gene expression profiles of 27 CCRCCs and 9 normal kidney tissues as well as 15 various adult normal tissues were examined by Affymetrix U133 Plus 2.0 arrays. Among the 34 genes specifically up-regulated in CCRCC, overexpression of Toll-like receptor 3 (TLR3) mRNA and its protein was validated by quantitative reverse transcription-PCR, immunoblot, and immunohistochemistry. The effects of TLR3 signaling on in vitro cell growth were examined.
  
  
  RESULTS
  TLR3 gene was highly expressed in CCRCC, with only limited expression in a panel of normal tissues. On immunohistochemical analysis using a monoclonal antibody against TLR3, overexpression of TLR3 was observed in 139 of 189 (73.5%) cases of CCRCC as well as in lung metastatic CCRCC (6 of 8), whereas TLR3 expression was entirely absent in chromophobe RCC (0 of 8). Polyinosinic-polycytidilic acid, a TLR3 ligand, exerted a growth-inhibitory effect against RCC cells in a TLR3-dependent manner. Moreover, a combination of polyinosinic-polycytidilic acid and IFNalpha exerted a synergistic growth-inhibitory effect against Caki-1 RCC cells.
  
  
  CONCLUSIONS
  This is the first report that TLR3 is overexpressed in CCRCC. These observations suggest that TLR3 pathway may represent a novel therapeutic target in CCRCC.
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ota
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kashima
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Tomita
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism*; D015195:Drug Design; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000378:metabolism / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D007369:Interferon Inducers; D051196:Toll-Like Receptor 3; D011070:Poly I-C