Prosaptide TX14A stimulates growth, migration, and invasion and activates the Raf-MEK-ERK-RSK-Elk-1 signaling pathway in prostate cancer cells.

Abstract

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.

• Authors: Shahriar Koochekpour, Oliver Sartor, Tae-Jin Lee, Arthur Zieske, David Y Patten, Masao Hiraiwa, Konrad Sandhoff, Natascha Remmel, Ardalan Minokadeh
• Journal: The Prostate (Prostate) Vol. 61 Issue 2 Pg. 114-23 (Oct 01 2004) ISSN: 0270-4137 [Print] United States
• PMID: 15305334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Wiley-Liss, Inc

Chemical References

• Glycoproteins
• Nerve Growth Factors
• PSAP protein, human
• Saposins
• prosaptide

Topics

• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Glycoproteins (metabolism)
• Humans
• MAP Kinase Signaling System (drug effects)
• Male
• Neoplasm Invasiveness (physiopathology)
• Nerve Growth Factors (pharmacology)
• Prostatic Neoplasms (metabolism, pathology, physiopathology)
• Saposins