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.
- Author:
Shahriar KOOCHEKPOUR
1
;
Oliver SARTOR
;
Masao HIRAIWA
;
Tae-Jin LEE
;
Walter RAYFORD
;
Natascha REMMEL
;
Konrad SANDHOFF
;
Ardalan MINOKADEH
;
David Y PATTEN
Author Information
- Publication Type:Journal Article
- MeSH: Cell Division; drug effects; Enzyme Activation; Humans; Male; Mitogen-Activated Protein Kinases; metabolism; Neoplasm Invasiveness; Prostatic Neoplasms; enzymology; metabolism; pathology; Receptors, Cell Surface; genetics; Receptors, Urokinase Plasminogen Activator; Reverse Transcriptase Polymerase Chain Reaction; Saposins; pharmacology; Signal Transduction; Stromal Cells; enzymology; metabolism; pathology; Up-Regulation; Urokinase-Type Plasminogen Activator; genetics
- From: Asian Journal of Andrology 2005;7(2):147-158
- CountryChina
- Language:English
-
Abstract:
AIMTo 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.
METHODSWe 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.
RESULTSSaposin 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.
CONCLUSIONSaposin 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.