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

doi:10.1038/bjc.2015.74

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

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 language	English
Pages (from-to)	1340 - 1348
Number of pages	9
Journal	British Journal of Cancer
Volume	112
Issue number	8
DOIs	https://doi.org/10.1038/bjc.2015.74
Publication status	Published - 2015

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Mahon, K. L., Lin, H-M., Castillo, L., Lee, B. Y., Lee-Ng, K. K. M., Chatfield, M. D., Chiam, K. H., 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. (2015). Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer. British Journal of Cancer, 112(8), 1340 - 1348. https://doi.org/10.1038/bjc.2015.74

Mahon, K L ; Lin, Hui-Ming ; Castillo, Lesley ; Lee, Brian Y ; Lee-Ng, Ka Ki Michelle ; Chatfield, Mark D ; Chiam, Karen HuiQin ; Breit, Samuel N ; Brown, David A ; Molloy, Mark P ; Marx, Gavin M ; Pavlakis, Nick ; Boyer, M J ; Stockler, Martin R ; Daly, Roger J ; Henshall, Susan M ; Horvath, Lisa G. / Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer. In: British Journal of Cancer. 2015 ; Vol. 112, No. 8. pp. 1340 - 1348.

@article{03c22db7f3b34be6b1ae1e1bac8a1ac4,

title = "Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer",

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",

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

year = "2015",

doi = "10.1038/bjc.2015.74",

language = "English",

volume = "112",

pages = "1340 -- 1348",

journal = "British Journal of Cancer",

issn = "0007-0920",

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Mahon, KL, Lin, H-M, Castillo, L, Lee, BY, Lee-Ng, KKM, Chatfield, MD, Chiam, KH, Breit, SN, Brown, DA, Molloy, MP, Marx, GM, Pavlakis, N, Boyer, MJ, Stockler, MR, Daly, RJ, Henshall, SM & Horvath, LG 2015, 'Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer', British Journal of Cancer, vol. 112, no. 8, pp. 1340 - 1348. https://doi.org/10.1038/bjc.2015.74

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

In: British Journal of Cancer, Vol. 112, No. 8, 2015, p. 1340 - 1348.

Research output: Contribution to journal › Article › Research › peer-review

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T1 - Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer

AU - Mahon, K L

AU - Lin, Hui-Ming

AU - Castillo, Lesley

AU - Lee, Brian Y

AU - Lee-Ng, Ka Ki Michelle

AU - Chatfield, Mark D

AU - Chiam, Karen HuiQin

AU - Breit, Samuel N

AU - Brown, David A

AU - Molloy, Mark P

AU - Marx, Gavin M

AU - Pavlakis, Nick

AU - Boyer, M J

AU - Stockler, Martin R

AU - Daly, Roger J

AU - Henshall, Susan M

AU - Horvath, Lisa G

PY - 2015

Y1 - 2015

N2 - 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

AB - 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

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U2 - 10.1038/bjc.2015.74

DO - 10.1038/bjc.2015.74

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