Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer

K L Mahon, Hui-Ming Lin, Lesley Castillo, Brian Y Lee, Ka Ki Michelle Lee-Ng, Mark D Chatfield, Karen HuiQin Chiam, Samuel N Breit, David A Brown, Mark P Molloy, Gavin M Marx, Nick Pavlakis, M J Boyer, Martin R Stockler, Roger J Daly, Susan M Henshall, Lisa G Horvath

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34 Citations (Scopus)

Abstract

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, approximately 50 of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1beta, IL-4, IL-6, IL-12 and IFNgamma) after cycle 1 of docetaxel were associated with progressive disease (all P
Original languageEnglish
Pages (from-to)1340 - 1348
Number of pages9
JournalBritish Journal of Cancer
Volume112
Issue number8
DOIs
Publication statusPublished - 2015

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