Nicholas Don-Doncow1, Felicia Marginean2, Ilsa Coleman3, Peter S Nelson3, Roy Ehrnström4, Agnieszka Krzyzanowska1, Colm Morrissey5, Rebecka Hellsten1, Anders Bjartell6. 1. Department of Translational Medicine, Division of Urological Cancers, Lund University, Malmö, Sweden. 2. Department of Translational Medicine, Division of Urological Cancers, Lund University, Malmö, Sweden; University and Regional Laboratories, Department of Pathology, Skåne University Hospital, Malmö, Sweden. 3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 4. University and Regional Laboratories, Department of Pathology, Skåne University Hospital, Malmö, Sweden. 5. Department of Urology, University of Washington, Seattle, WA, USA. 6. Department of Translational Medicine, Division of Urological Cancers, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Lund University, Malmö, Sweden. Electronic address: anders.bjartell@med.lu.se.
Abstract
STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC. PATIENT SUMMARY: We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs.
STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC. PATIENT SUMMARY: We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs.
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