We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.
- Authors
Mahon, K L; Lin, H-M; Castillo, L; Lee, B Y; Lee-Ng, M; Chatfield, M D; Chiam, K; Breit, S N; Brown, D A; Molloy, M P; Marx, G M; Pavlakis, N; Boyer, M J; Stockler, M R; Daly, R J; Henshall, S M; Horvath, L G
- Abstract
Background:Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼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-1β, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002).Conclusions:In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.
- Subjects
PROSTATE cancer; CYTOKINES; DOCETAXEL; DRUG resistance in cancer cells; COHORT analysis; MONOCYTES
- Publication
British Journal of Cancer, 2015, Vol 112, Issue 8, p1340
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/bjc.2015.74