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

Shahriar Koochekpour, Oliver Sartor, Tae Jin Lee, Arthur W. Zieske, David Y. Patten, Masao Hiraiwa, Konrad Sandhoff, Natascha Remmel, Ardalan Minokadeh

Research output: Contribution to journalArticle

21 Scopus citations

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-MEKERK-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.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalProstate
Volume61
Issue number2
DOIs
StatePublished - Oct 1 2004

Keywords

  • MAPK
  • Prosaposin
  • Prosaptide TX14A
  • Prostate cancer
  • Saposin C

ASJC Scopus subject areas

  • Oncology
  • Urology

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