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Sharma et al. The role of SPARC in reactivation of prostate cancer cells in bone
DOI:10.1038/bonekey.2016.91
Sharma et al. isolated two prostate cancer cell lines both of which grew at similar rates in vitro but which behaved very differently in vivo. By characterizing and comparing the indolent cell and its aggressive counterpart, the authors identified key factors that appear to drive bone reactivation of prostate cancer cells in the bone microenvironment.
The less aggressive indolent cell was show to produce secreted protein acidic and rich in cysteine (SPARC). This stimulated bone marrow stromal cells to express BMP7, which then kept the cells in a state of dormancy. In contrast, the more aggressive cell line produced no SPARC as it had been epigenetically silenced by promoter methylation. Treatment with 5-azacytidine reactivated SPARC expression and re-established dormancy.
The authors also demonstrated that NS398, a COX2 inhibitor, acted to reduce expression of de novo DNA methylases and to increase expression of SPARC, suppressing tumor growth in bone cultures.
The role of SPARC in human patients was also examined and men whose cancer cells showed promoter methylation and so silencing of SPARC expression had shorter periods of disease-free survival.
Editor’s comment: Molecular mechanisms by which cancer cells enter a dormant state are poorly understood. The identification of mediators of metastatic latency such as SPARC (and BMP7) will help to develop strategies aimed at preventing metastasis.
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