Prostate cancer survival protein also involved in metastasis
MedWire News: Researchers have shown that the signal transducer and activator of transcription 5 protein (Stat5) is involved in the metastasis of human prostate cancer.
“Until now, we thought that Stat5 was involved in primarily promoting tumor growth, but this study indicates it could be one of the key players in pushing prostate cancer to spread,” said author Marja Nevalainen from Thomas Jefferson University in Philadelphia, Pennsylvania, USA.
Nevalainen and colleagues’ used in vitro and in vivo models to show that the majority of Stat5-regulated genes are metastases-related, that Stat5 increases the migration of human prostate cancer cells, and, importantly, Stat5 increases the metastatic potential of prostate cancer cells in vivo.
Although the normal function of Stat5 is unknown, previous studies have demonstrated that inhibition of Stat5 results in rapid and massive apoptosis of prostate cancer cells, remarks the research team.
In the current study, they analyzed tissue from 128 metastasized prostate cancer cases and found Stat5 to be active in 61% of cases, including 81% of lymph node and 33% of bone metastases.
The team then infected the prostate cancer cell lines DU145 and PC-3 with Stat5, and observed that cell migration increased by up to 60% compared with non-Stat5-infected cells.
Gene expression profiling revealed a 777-gene difference between Stat5-negative DU145 and Stat5-positive DU145 cells. Of these genes, 21.0% were related to metastases, while 7.9% were related to proliferation, and 3.9% to apoptosis.
Of note, after injecting nude mice with Stat5-infected DU145 prostate cancer cells, the number of lung metastases increased by approximately 11-fold, compared with mice injected with β-galactosidase-expressing DU145 cells.
“This is the first demonstration that Stat5 increases the intrinsic ability of prostate cancer cells to metastasize in vivo,” write Nevalainen and colleagues in the journal Endocrine-Related Cancer.
Nevalainen added: “This result is important because laboratory observations on invasiveness or migration of cells in culture do not necessarily translate into cells having the ability to metastasize in animals.”
The team speculates that the molecular mechanisms underlying increased metastases formation with active Stat5 are likely to include heterotypic adhesion of prostate cancer cells to epithelial cells, and decreased cell surface epithelial-cadherin, which plays an important role in cell adhesion.
They conclude: “Stat5a/b may provide a therapeutic target protein specifically for advanced disseminated prostate cancer.”
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By Sarah Guy