Prosaptide TX14A stimulates growth, migration, and invasion and activates the Raf-MEK-ERK-RSK-Elk-1 signaling pathway in prostate cancer cells.
BACKGROUND
Prosaposin is a neurotrophic factor. Prosaposin knock-out mice have been reported to develop a number of abnormalities, including atrophy of the prostate gland and mitogen-activated protein kinase (MAPK)-inactivation in prostate epithelial cells. These abnormalities underscore a potential fundamental role in prostate development. The trophic factor activity of prosaposin has been localized at a specific amino terminal portion of the molecule that has been the source for a number of biologically active peptides called prosaptides (e.g., TX14A). The expression and function of prosaposin in prostate cancer is not known.


METHODS
Using conventional protein expression analysis, immunohistochemical staining, cell proliferation assays, and in vitro invasion assays, we determined the expression of prosaposin and the effect of prosaptide TX14A on cell growth/death protection, motility, invasion, and MAPK signal transduction pathway in prostate cancer cells.


RESULTS
We found a higher expression of prosaposin in androgen-independent (AI) prostate cancer cells (PC-3 and DU-145) than in androgen-dependent (AD) LNCaP or normal prostate epithelial cells. Immunohistochemical staining on benign and malignant prostate tissues revealed an intense cytoplasmic anti-prosaposin immunoreactivity in tumor cells, as well as stromal, endothelial, and inflammatory mononuclear cells. The intensity of staining was proportional to the overall Gleason's score. In addition, we demonstrated that TX14A stimulates cell proliferation/survival, migration, and invasion, and activates the Raf-MEK-ERK-RSK-Elk-1 signaling cascade of the MAPK pathway.


CONCLUSIONS
These results are suggestive of a potential pleuripotent regulatory function for prosaposin in prostate cancer.
Department of Microbiology, Immunology, and Parasitology, Louisiana State University-Health Sciences Center, New Orleans, Louisiana, USA. skooch@lsuhsc.edu
Shahriar
S
Koochekpour
Oliver
O
Sartor
Tae-Jin
TJ
Lee
Arthur
A
Zieske
David Y
DY
Patten
Masao
M
Hiraiwa
Konrad
K
Sandhoff
Natascha
N
Remmel
Ardalan
A
Minokadeh
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D049231:Saposins
D006023:Glycoproteins; D009414:Nerve Growth Factors; C483345:PSAP protein, human; D049231:Saposins; C101246:prosaptide