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Frame et al. Investigating models for prostate cancer research

observe cell behavior in real-time and to detect any DECLARATIONS
inherently resistant cells within the heterogeneous
primary cultures. Acknowledgments
Our sincere appreciation goes to the patients from
Going forward, using primary prostate epithelial Castle Hill Hospital, Cottingham, for providing prostate
cultures, as part of the lab to clinic pipeline, has tissue, and also goes to Prof. Simon Hayward for
many advantages including patient variation, current BPH-1 cells.
and follow-up pathology, correlation with patient
outcome, representation of modern disease, close- Authors’ contributions
to-patient, clinically relevant and less adapted to Conceived the overall study and wrote the manuscript:
tissue culture conditions than cell lines. The model is F.M. Frame
also flexible since the cultures with typically a basal Designed the graphics in Figures 1 and 6 and executed
phenotype can be pushed to differentiate and express the work in Figure 2: F.M. Frame
luminal markers [40,41] and 3D spheroid culture is also Conceived and executed the experiments in Figures 4
possible [42] . Even in the 2D culture, microenvironment and 5: F.M. Frame, A.R. Noble
studies can be carried out using the STO feeder Provided technical expertise integral to completion of
cells as a stromal mimic. This technique has been the experimental works: H.F. Walker
used to elegant effect, where STO feeder cells were Conceived and carried out the data in Figure 3: S. Klein
engineered to express human IL-4, and this resulted Provided technical expertise for the Quantitative Phase
in an increase in clonogenic potential of primary Imaging work: R. Suman, R. Kasprowicz
prostate epithelial cells through the STAT6 signaling Arranged permission, collection and delivery of patient
pathway . samples: V.M. Mann
[43]
Provided patient material and be the liaison between
Several recent studies using primary prostate the laboratory and the clinic: M.S. Simms
epithelial cultures have shown the heterogeneity of Oversaw all work and was awarded the funding for this
response to current and novel treatments including study: N.J. Maitland
autophagy [20,26] , necrosis [27] , cell differentiation [44,45] ,
apoptosis, DNA damage [15,27] , cell cycle arrest and Financial support and sponsorship
senescence [20] [Figure 6]. Several of these can act as FMF, ARN, HFW and VMM are funded by a PCUK
a crossroads for a cell resulting in cell survival or cell Innovation Award - RIA15-ST2-022. SK was supported
death and if we are able to predict which response by a White Rose Fund studentship.
may occur then we may be able to manipulate it
towards cell death. It is not appropriate to totally Conflicts of interest
rely on endpoint assays; we cannot be satisfied with RK and RS are employees of PhaseFocus Ltd. This
a 90% reduction in cell viability without questioning company has provided the VL21 microscope for use
what is happening in the other 10% of cells, and by FMF and AN. RK and RS have provided technical
indeed characterizing these cells relative to the knowledge and support.
whole population. If we can identify mechanisms of
resistance in bulk populations as well as rare cell Patient consent
populations we will be more able to design biologically Patients gave informed consent and all patient samples
relevant combination treatments. In addition, there were anonymized.
shouldn’t be too much reliance on a single model.
All models have their advantages and limitations; the Ethics approval
important thing is to acknowledge them rather than Patient samples were collected with ethical permission
to ignore them. In terms of primary prostate cultures, from Castle Hill Hospital (Cottingham, Hull) (Ethics
heterogeneity provides an advantage to testing Number: 07/H1304/121). Use of patient tissue was
therapies rather than a confounding factor. If we are approved by the Local Research Ethics Committees.
able to use techniques such as QPI to measure each
individual cell as a data point we should be able to REFERENCES
tease apart the variation in cell responses to different
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2013;5:25-40.
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clinical trials. 3. Barbieri CE, Demichelis F, Rubin MA. Molecular genetics of prostate
312 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ December 6, 2017