title: Expression and Function of LPA1 in Bladder Cancer.
abstract: OBJECTIVE
  LPA is one of several physiologically active lipid mediators that promote cell proliferation and invasion, and are present in serum, ascites and urine. LPA receptor is a G-protein coupled receptor that is considered a potential therapeutic target for some malignant cancers. We evaluated the expression of LPA receptors in bladder cancer and the effect of LPA in bladder cancer invasion.
  
  
  METHODS
  Using real-time polymerase chain reaction and immunohistochemical staining we determined LPA receptor expression in bladder cancer specimens from patients with bladder cancer, including 12 with Ta or T1 and 15 with T2-T4 disease. ROCK expression, myosin light chain phosphorylation and Matrigel™ invasion assays were done and morphological observations were made to assess LPA effects in T24 cells, which were derived from bladder cancer.
  
  
  RESULTS
  Notably LPA1 mRNA expression was significantly higher in muscle invasive bladder cancer specimens than in nonmuscle invasive specimens. Strong LPA1 expression was evident on cell membranes in muscle invasive specimens. T24 cell invasion was increased by LPA treatment and invasiveness was decreased by LPA1 siRNA or LPA1 inhibitor. LPA treatment increased ROCK1 expression and myosin light chain phosphorylation, and induced morphological changes, including lamellipodia formation and cell rounding.
  
  
  CONCLUSIONS
  Results indicate that LPA signaling via LPA1 activation promoted bladder cancer invasion. LPA1 might be useful to detect bladder cancer with highly invasive potential and become a new therapeutic target for invasive bladder cancer treatment.
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan. Electronic address: masaoka@fmu.ac.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kumagai
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yanagida
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Aikawa
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Chiba
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan; Department of Pathology (HC), Fukushima Medical University, Fukushima, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery
chemical_list: D049368:Receptors, Lysophosphatidic Acid
keywords: G-protein-coupled; lysophosphatidic acid; neoplasm invasiveness; receptors; rho-associated kinases; urinary bladder neoplasms