title: Expression of CX3CR1 associates with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma.
abstract: OBJECTIVE
  The identification of critical proteins regulating cancer cell metastasis, in clear cell renal cell carcinoma (CCRCC), is important for prediction of prognosis, prevention of metastasis, and treatment of this lethal malignancy. In the present study, we evaluated the role of CX3CR1 in cellular adhesion, migration, and metastasis in CCRCC. We further investigated the downstream molecular signaling mechanism of fractalkine (FKN)-CX3CR1-induced migration and metastasis.
  
  
  METHODS
  The expression and localization of CX3CR1 in RCC cell lines were assessed by immunofluorescence analysis. The migration of cancer cells was examined by wound healing and transwell migration assay. The expression level of CX3CR1 and FKN in 78 CCRCC individual samples, 16 normal kidney cortex tissue samples, and 16 cases of metastatic lesions of CCRCC were evaluated using immunohistochemical analysis on tissue microarray. The signal pathway of functional FKN was analyzed by the use of the western-blotting method and inhibitory migration assay.
  
  
  RESULTS
  CX3CR1 was expressed in human RCC cell lines, and only membrane positive cells were responsible for FKN-induced cell migration. Extracellular signal-related kinases (ERK1/2) and phosphatidyl-inositide 3 kinase/Akt (PI3K/Akt) were each activated upon soluble FKN stimulation in a time-dependent manner, whereas blockades of MEK, PI3K, and G proteins prevented FKN-mediated cellular migration. Furthermore, CCRCC tissue microarray immunohistochemistry data revealed a clear association of strong CX3CR1 expression with tumor metastasis and poor prognosis.
  
  
  CONCLUSIONS
  CX3CR1 expression is associated with the process of cellular migration in vitro and tumor metastasis of CCRCC in vivo. Both clinical and molecular cellular evidence suggest that CX3CR1 is a potential marker and therapeutic target for CCRCC prognostic prediction and treatment.
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: yaoxin1969@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Zhenting
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Suxiang
authors.initials: S
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D054428:Chemokine CX3CL1 / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: CX3CR1; Clear cell renal cell carcinoma; Fractalkine; Metastasis; Migration; Prognosis