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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
Calcitriol inhibits growth response to Platelet-Derived Growth Factor-BB in human prostate cells
Nadja Nazarova1, Olga Golovko, Merja Bläuer
1Department of Anatomy, Medical School, University of Tampere, 33014 Tampere, Finland. nadya.nazarova@uta.fi
Abstract:
Calcitriol, a hormonal form of Vitamin D, regulates growth of normal and cancer cells of various origins by modulation of peptide growth factors signaling. Platelet-Derived Growth Factor (PDGF) signaling pathway is involved in prostate cancer progression. We studied the expression of PDGF receptors in human prostate primary stromal cells and cancer epithelial cell lines and growth response to PDGF-BB isoform. We found that the expression of PDGF receptors and PDGF-BB-mediated cell growth are regulated by calcitriol in prostate cells. Quantitative RT-PCR analysis revealed a lower level of mRNA for PDGF receptors in LNCaP and PC-3 cells than in primary stromal cells. Western blotting showed a high amount of PDGFRalpha and beta proteins in primary stromal cells that could not be detected in LNCaP, which may explain the resistance of LNCaP cells to growth-promoting effect of PDGF-BB. Addition of Epidermal Growth Factor (EGF) to the culture medium induces the expression of PDGFRbeta and restores responsiveness of LNCaP to PDGF-BB to some extent. Calcitriol down-regulates PDGFRbeta expression and negatively regulates PDGF-mediated cell growth. Calcitriol does not affect PDGFRalpha and PDGF-B mRNA expression. We suggest that inhibition of PDGFRbeta expression by calcitriol might reduce responsiveness of prostate cells to mitogenic action of PDGF-BB.
Insights
Calcitriol, a form of Vitamin D, influences prostate cancer growth by regulating Platelet-Derived Growth Factor (PDGF) signaling. It down-regulates PDGFRbeta, potentially reducing prostate cell response to PDGF-BB, impacting cancer progression.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Calcitriol (Vitamin D) modulates cell growth and peptide growth factor signaling.
- Platelet-Derived Growth Factor (PDGF) signaling is implicated in prostate cancer progression.
Purpose of the Study:
- To investigate the role of calcitriol in regulating PDGF receptor expression and signaling in prostate cells.
- To determine the effect of calcitriol on prostate cancer cell growth response to PDGF-BB.
Main Methods:
- Quantitative RT-PCR to analyze mRNA levels of PDGF receptors.
- Western blotting to assess protein expression of PDGF receptors.
- Cell culture experiments to evaluate growth responses to PDGF-BB and Epidermal Growth Factor (EGF).
Main Results:
- Prostate cancer cell lines (LNCaP, PC-3) showed lower PDGF receptor mRNA than primary stromal cells.
- LNCaP cells expressed low PDGFRalpha and beta protein, correlating with resistance to PDGF-BB.
- Calcitriol down-regulated PDGFRbeta expression and inhibited PDGF-mediated cell growth.
- EGF partially restored LNCaP responsiveness to PDGF-BB by inducing PDGFRbeta.
Conclusions:
- Calcitriol regulates PDGF receptor expression and signaling in prostate cells.
- Calcitriol's down-regulation of PDGFRbeta may reduce prostate cancer cell responsiveness to PDGF-BB.
- Targeting PDGFRbeta with calcitriol could be a strategy to inhibit prostate cancer growth.
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