title: Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma.
abstract: BACKGROUND
  Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC).
  
  
  METHODS
  Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft.
  
  
  RESULTS
  We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis.
  
  
  CONCLUSIONS
  Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.
authors.affiliation: 1] Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China [2] Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Yen
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Vasgene Therapeutics Inc., Los Angeles, CA 90033, USA.
authors.forename: V
authors.initials: V
authors.lastname: Krasnoperov
authors.affiliation: The State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan 410078, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xia
authors.affiliation: 1] Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China [2] Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Urology, Campus Bio-Medico University, Rome 00128, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Bove
authors.affiliation: Department of Urology, Campus Bio-Medico University, Rome 00128, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Buscarini
authors.affiliation: Division of Surgery, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: D
authors.initials: D
authors.lastname: Parekh
authors.affiliation: Department of Urology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: I S
authors.initials: IS
authors.lastname: Gill
authors.affiliation: Department of Orthopedic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 41008, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tretiakova
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: D
authors.initials: D
authors.lastname: Quinn
authors.affiliation: Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Gill
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000094963:Axl Receptor Tyrosine Kinase