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Maitland Prostate cancer: from bench to bedside

Establishing a multidisciplinary team biopsy, the pathologist who decides the area for
Thus truly translational research requires an ability sampling, the research nurse, technician or tissue
to access fresh human cancer tissues, rather than procurement officer who takes the samples and finally
employ the current laboratory “formula” for medical the research team, who process and analyze the
research, where detailed experiments are performed sample (see below). Finally the clinical history of the
on cell lines, and then (often summarily) tested with patient is required to ensure that a particular patient
a number of patient samples for the same response who has been studied intensively is not an anomaly
in formalin fixed tissue for antigen expression. Is within the general patient population, or indeed has
this really valid as a critical assay of a longer term been subject to an initial misdiagnosis.
treatment for prostate cancers?
In many cases, a basic science investigation does
Certainly the availability of large numbers of tissue not fit within the National Health Service (NHS)
sections in array format should revolutionize the ethical framework (and paperwork) in the UK,
correlative part of such a study, but this resource is where the procedure is more often designed with a
not available to all, and is of variable quality between clinical trial of drug efficacy in patients, from whom
different sources and centers depending on the tissue/blood samples are required. The elapsed
time of surgery, fixation and processing required time from application to approval is also rather
to produce a grid of perhaps 96 disease-focused long and incompatible with some grant deadlines.
tissue sections. It is also largely dependent on the However, it remains essential to have such approval
skill of the histopathologist in obtaining the tumor in place before funding is approved. Again the
localized blocks. When fresh unfixed tumor biopsies multidisciplinary team (MDT) approach and closer
are required, this becomes just as much a multi- clinical science liaison is the best approach. Ethical
disciplinary team effort as the treatment of prostate compliance from the very start is not only desirable,
cancer. It involves the surgeon who removes the but essential now for many grant-giving bodies.
The complexities of tissue processing from
tissue biopsies
The next stage in the procedure involves the
processing of the tissues from primary samples. Over
many years my laboratory has developed the means
to fractionate prostate tissues into many constituent
cell types. This is illustrated in Figure 2. Although
individual populations can for example be studied in
isolation for a particular gene expression pattern or a
cancer target expression, this may not be the ultimate
analytical system in which to determine whether a
patient’s tumor is indeed susceptible to such treatment.
The mere act of dissociating the tissue biopsy could
be sufficient to modify gene expression in the short
term. For example, the stress of homogenisation
and the time taken may well affect individual gene
expression patterns/cell types. The loss of infiltrating
macrophages and lymphocytes from the tissues is
also of concern, given our current knowledge of their
influence on not only each other, but also on the whole
tumor micro-environment.

Therapeutic development strategies which involve
growing cells from prostate tissues in the laboratory are
inevitably a compromise. Purification of different cell
Figure 2: Selection of cells from prostate tissue. Protocols have types and their culture removes micro-environmental
been developed to extract, enrich and select different cell types influences. The mere induction of cell proliferation
from fresh human prostate tissue. The cell types include immune within a cell population also induces new patterns of
cells, stromal cells and epithelial cells. Luminal cells and basal
cells, which include transit amplifying progenitor cells, committed gene expression, as we have recently shown in benign
[24]
basal cells and stem cells, can be selected prostatic hyperplasia . Such a reductionist approach
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ November 17, 2017 265