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Volume 7, Issue 2 (March 2005) 7, 147–158; 10.1111/j.1745-7262.2005.00037.x
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
Shahriar Koochekpour, Oliver Sartor, Masao Hiraiwa, Tae-Jin Lee, Walter Rayford, Natascha Remmel, Konrad Sandhoff, Ardalan Minokadeh and David Y Patten
1.Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
2.Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
3.Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
4.Department of Urology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
5.Department of Neurosciences, University of California, San Diego, Center for Molecular Genetics, La Jolla, California 92093, USA
6.Kekulé-Institut fuer Organische Chemie Und Biochemie, Universitaet Bonn, D-53121 Bonn, Germany
Received: 2004-09-13 Accepted: 2005-01-31
| Abstract |
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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 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.
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.
Keywords: saposin C, prostate cancer uPA/uPAR, prosaposin, invasion, growth factor, SAPK/JNK, MAPK, MMP, c-Jun
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