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 (uP...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.展开更多
文摘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.
