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  

作　　者：Shahriar Koochekpour Oliver Sartor Masao Hiraiwa Tae-Jin Lee Walter Rayford Natascha Remmel Konrad Sandhoff ArdalanMinokadeh DavidY.Patten 

机构地区：[1]Department of Microbiology,Immunology and Parasitology, Stantey S.Scott Cancer Center, [2]Stanley S.Scott Cancer Center, Department of Medicine [3]Department of Neurosciences,University of California,San Diego,Center for Molecular Genetics,La Jolla,California 92093,USA [4]Department of Microbiology,Immunology and Parasitology, Stanley S.Scott Cancer Center, [5]Department of Urology,Louisiana State University Health Sciences Center,New Orleans,Louisiana 70112,USA [6]Kekul■-Institut fuer Organische Chemie Und Biochemie,Universitaet Bonn,D-53121 Bonn,Germany [7]Department of Microbiology,Immunology and Parasitology, Stanley S.Scott Cancer Center

出　　处：《Asian Journal of Andrology》2005年第2期147-158, ,共12页亚洲男性学杂志（英文版）

摘　　要：Aim: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 NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.Methods:We employed West- ern 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.Conclusion: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.Aim: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 NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.Methods:We employed West- ern 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.Conclusion: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.

关 键 词：saposin C prostate cancer UPA/UPAR PROSAPOSIN INVASION growth factor SAPK/JNK MAPK MMP c-Jun 

分 类 号：R737.25[医药卫生—肿瘤]