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Updated: May 12, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Exogenous SPARC suppresses proliferation and migration of prostate cancer by interacting with integrin β1
Minkyoung Shin1, Atsushi Mizokami, Jungim Kim
1Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
Background:
The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear.
Methods:
To identify SPARC protein in prostate tissue, immunohistochemical analysis of SPARC was conducted using human prostate tissue microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC-3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was confirmed by western blot analysis after coculture with stromal cells. Proliferation and migration of PCa cells were examined by addition of SPARC. The interaction between SPARC and integrin β1 was confirmed by western blot analysis after immunoprecipitation.
Results:
SPARC protein was expressed well in normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed interaction of SPARC and integrin β1 in PCa cells. Inhibited proliferation and migration of PCa cells by SPARC was restored by integrin β1 neutralizing antibody.
Conclusions:
Reduced SPARC secretion from stromal cells might affect PCa progression mediating through limiting AKT phosphorylation after interaction with integrin β1.
Insights
Reduced secreted protein acidic and rich in cysteine (SPARC) in prostate cancer (PCa) stromal cells may promote tumor progression. SPARC limits AKT phosphorylation via integrin β1, inhibiting PCa cell proliferation and migration.
Area of Science:
- Oncology
- Cancer Biology
- Cellular Signaling
Background:
- The matricellular protein secreted protein acidic and rich in cysteine (SPARC) is implicated in tumor metastasis and progression across various cancers.
- The specific role of SPARC in prostate cancer (PCa) pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the expression and function of SPARC in prostate cancer.
- To elucidate the molecular mechanisms by which SPARC influences PCa cell behavior and progression.
Main Methods:
- Immunohistochemistry was used to assess SPARC protein levels in human prostate tissues.
- RT-PCR, Western blot, and ELISA were employed to detect SPARC expression in PCa and stromal cells.
- Functional assays, including AKT phosphorylation, proliferation, and migration studies, were performed to evaluate SPARC's impact on PCa cells, with co-culture and immunoprecipitation experiments to explore interactions.
Main Results:
- SPARC protein expression was notably higher in normal prostate tissue compared to PCa tissue.
- Normal prostate-derived stromal cells (PrSC) secreted significantly more SPARC than PCa-derived stromal cells (PCaSC) or PCa cells.
- SPARC treatment or co-culture with PrSC reduced AKT phosphorylation in PCa cells, while SPARC knockdown in PrSC restored phosphorylation. SPARC interacted with integrin β1, and this interaction mediated the inhibition of PCa cell proliferation and migration.
Conclusions:
- Decreased SPARC secretion by stromal cells may contribute to prostate cancer progression.
- This progression is potentially mediated by SPARC limiting AKT phosphorylation through its interaction with integrin β1.
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