SRPK2 May Have Key Role in Prostate Cancer Progression and Metastasis
Key findings
- Expression of SRPK2 was greater in human prostate cancer tissues than in noncancerous tissues
- High expression of SRPK2 was significantly correlated with higher tumor grade, advanced pathological stage and the presence of metastasis
- The biochemical recurrence-free time of prostate cancer patients with high SRPK2 expression was significantly shorter than that of patients with low expression
- Experiments in human prostate cancer cell lines demonstrated that higher SRPK2 expression promoted cell proliferation, migration ability, invasive ability and cell-cycle progression; conversely, it suppressed tumor cell apoptosis
- In xenograft experiments with mice, SRPK2 promoted prostate tumor growth
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Currently, there is no effective treatment for patients with prostate cancer who experience biochemical recurrence, castrate-resistant disease or metastasis. To gain insight into how to prevent aggressive disease, scientists are working to identify the molecular mechanisms of prostate cancer progression and metastasis.
Serine/arginine–rich (SR) proteins and their protein-specific kinases (SRPKs) are associated with pre-mRNA splicing dysregulation in various tumor types, including prostate cancer. In particular, SRPK2 is known to promote cancer cell growth and migration.
Recently Chin-Lee Wu, MD, PhD, associate pathologist at Massachusetts General Hospital, and colleagues reported for the first time that SRPK2 is involved in prostate cancer. They published their findings in Biomedicine & Pharmacotherapy.
SRPK2 Upregulated in Prostate Cancer Tissues
In a microarray with prostate tissue samples from 80 patients, which included 73 patients with prostate cancer who had radical prostatectomy, one patient with benign prostate hyperplasia and six healthy men, Dr. Wu's team found that expression of SRPK2 protein in prostate cancer tissues was significantly higher than in adjacent benign prostate tissues. They made similar observations when evaluating public microarray datasets using the Oncomine.org cancer database.
SRPK2 Associated with Progression, Metastasis and Unfavorable Prognosis
Using the tissue microarray, the team observed that SRPK2 expression significantly increased as tumor grade increased, for Gleason scores ≥8. Greater SRPK2 staining was also significantly associated with a more advanced pathological stage.
In a dataset of mRNA microarray expression data and accompanying clinical information from the Cancer Genome Atlas, they found that, likewise, increased SRPK2 expression was significantly associated with patient age, higher Gleason score, advanced pathological stage and presence of metastasis.
High versus low SRPK2 expression significantly predicted shorter biochemical recurrence-free survival.
SRPK2 Affected Progression and Metastasis
Next, the research group transfected three different human prostate cancer cell lines with an SRPK2-overexpressing plasmid. The proliferative ability of the SRPK2-overexpressing cells was significantly increased compared with groups of control cells.
Furthermore, in all three cell lines, overexpression of SRPK2 significantly promoted migration ability, invasive ability and cell-cycle progression when compared with control cells. Rates of apoptosis were significantly lower for the SRPK2-overexpressing cell lines than for the controls.
SRPK2 Promoted Tumor Growth in Xenograft Experiments
Using one of the human prostate cancer cell lines, the researchers injected SRPK2-transfected cells and control cells into nude mice. Tumors generated from the SRPK2-overexpressing cells grew faster than those from the control group and were larger after four weeks.
Dr. Wu's team concludes that SRPK2 seems to play an important role in prostate cancer progression and metastasis and might provide valuable knowledge about how to prevent progression and improve diagnosis. For further exploration of SRPK2, they suggest angiogenesis experiments, studies in a knockout mouse model and studies in a mouse model of castration-resistant prostate cancer.
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