دورية أكاديمية
Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma.
| العنوان: | Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma. |
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| المؤلفون: | Armstrong CWD; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Coulter JA; School of Pharmacy, Queen's University Belfast, Belfast, BT9 7AE, UK., Ong CW; Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre, Singapore, 169610., Maxwell PJ; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Walker S; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Butterworth KT; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Lyubomska O; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Berlingeri S; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Gallagher R; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., O'Sullivan JM; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Jain S; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Mills IG; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Prise KM; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Bristow RG; Movember FASTMAN Centre of Excellence, Manchester CRUK Institute, Manchester, SK10 4TG, UK., LaBonte MJ; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK., Waugh DJJ; Movember FASTMAN Centre of Excellence, Patrick G Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7AE, UK. |
| المصدر: | NAR cancer [NAR Cancer] 2020 Sep; Vol. 2 (3), pp. zcaa012. Date of Electronic Publication: 2020 Jul 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101769553 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2632-8674 (Electronic) Linking ISSN: 26328674 NLM ISO Abbreviation: NAR Cancer Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford : Oxford University Press, [2019]- |
| مستخلص: | Functional impairment of the tumour suppressor PTEN is common in primary prostate cancer and has been linked to relapse post-radiotherapy (post-RT). Pre-clinical modelling supports elevated CXC chemokine signalling as a critical mediator of PTEN -depleted disease progression and therapeutic resistance. We assessed the correlation of PTEN deficiency with CXC chemokine signalling and its association with clinical outcomes. Gene expression analysis characterized a PTEN LOW /CXCR1 HIGH /CXCR2 HIGH cluster of tumours that associates with earlier time to biochemical recurrence [hazard ratio (HR) 5.87 and 2.65, respectively] and development of systemic metastasis (HR 3.51). In vitro , CXCL signalling was further amplified following exposure of PTEN -deficient prostate cancer cell lines to ionizing radiation (IR). Inhibition of CXCR1/2 signalling in PTEN- depleted cell-based models increased IR sensitivity. In vivo , administration of a CXCR1/2-targeted pepducin (x1/2pal-i3), or CXCR2-specific antagonist (AZD5069), in combination with IR to PTEN -deficient xenografts attenuated tumour growth and progression compared to control or IR alone. Post-mortem analysis confirmed that x1/2pal-i3 administration attenuated IR-induced CXCL signalling and anti-apoptotic protein expression. Interventions targeting CXC chemokine signalling may provide an effective strategy to combine with RT in locally advanced prostate cancer patients with known presence of PTEN -deficient foci. (© The Author(s) 2020. Published by Oxford University Press on behalf of NAR Cancer.) |
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| معلومات مُعتمدة: | MR/J007641/1 United Kingdom MRC_ Medical Research Council |
| تواريخ الأحداث: | Date Created: 20200804 Latest Revision: 20210120 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7380483 |
| DOI: | 10.1093/narcan/zcaa012 |
| PMID: | 32743555 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2632-8674 |
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| DOI: | 10.1093/narcan/zcaa012 |