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Heterogeneous copper concentrations in cancerous human prostate tissues

journal contribution
posted on 2023-10-26, 03:20 authored by Delphine Denoyer, Sharnel Clatworthy, Shashank Masaldan, Peter Meggyesy, Michael Cater
BACKGROUND: Therapeutics that target copper for the treatment of prostate cancer are being evaluated in human clinical trials. Elevated intracellular copper is considered to sensitize prostate cancer cells to certain copper-coordination compounds, especially those with ionophoric properties. While there is compelling in vitro evidence that prostate cancer cells accumulate intracellular copper, a corresponding status for copper in patient tissues has not been corroborated. We therefore established whether copper concentrations increase in cancerous prostate tissues, and in sera, in patients throughout disease progression. METHODS: Human prostate tissue samples were obtained from patient prostatectomies (n = 28), and together with patient-matched sera, were analyzed for copper content by inductively coupled plasma mass spectrometry. RESULTS: When grouped together, cancerous prostate tissues exhibiting moderate disease severity (Gleason Score 7) (n = 10) had 1.6-fold more copper than age-matched normal tissues (n = 10) (P < 0.05). Those with more aggressive disease (Gleason Score 9) (n = 8) had 1.8-fold more copper (P < 0.05). In both disease stages however, the copper concentrations between individual samples were rather variable (0.55-3.02 μg/g), with many clearly within the normal range (0.52-1.28 μg/g). Additionally, we found that there was no change in serum copper concentrations in patients with either moderate or aggressive prostate cancer (Gleason Score 7 or 9), compared with reference intervals and to age-matched controls. CONCLUSIONS: The heterogeneous nature of copper concentrations in cancerous prostate tissues, suggest that a small subset of patients may respond to treatments that target elevated intratumoral copper. Therefore, such approaches would likely require personalized treatment strategies.

History

Journal

Prostate

Volume

75

Pagination

1510 - 1517

Location

London, Eng.

ISSN

0270-4137

eISSN

1097-0045

Language

eng

Publication classification

C Journal article; C1 Refereed article in a scholarly journal

Copyright notice

2015, Wiley Periodicals