title: Saposin C stimulates growth and invasion, activates p42/44 and SAPK/JNK signaling pathways of MAPK and upregulates uPA/uPAR expression in prostate cancer and stromal cells.
abstract: OBJECTIVE
  To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation, migration and invasion, as well as its effect on the expression of urokinase plasmonogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate cells. In addition, we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.
  
  
  METHODS
  We employed Western blot analysis, phospho-specific antibodies, cell proliferation assay, reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer cells.
  
  
  RESULTS
  Saposin C, in a cell type-specific manner, upregulates uPA/uPAR and immediate early gene c-Jun expression, stimulates cell proliferation, migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer cells. Normal prostate epithelial cells were not responsive to saposin C treatment in the above studies.
  
  
  CONCLUSIONS
  Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal cells. These results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 4-17, New Orleans, LA 70112, USA. skooch@lsuhsc.edu
authors.forename: Shahriar
authors.initials: S
authors.lastname: Koochekpour
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: Masao
authors.initials: M
authors.lastname: Hiraiwa
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Walter
authors.initials: W
authors.lastname: Rayford
authors.forename: Natascha
authors.initials: N
authors.lastname: Remmel
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Ardalan
authors.initials: A
authors.lastname: Minokadeh
authors.forename: David Y
authors.initials: DY
authors.lastname: Patten
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049231:Saposins / Q000494:pharmacology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D049231:Saposins; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator