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Falconer et al. MT-MMPs in prostate cancer

MMP-1 expression has been associated with lower immunohistochemistry and compared prostate
grade prostate tumors. In this section, we have intraepithelial neoplasia (PIN) and its normal adjacent
summarised the clinical expression data available for prostate (NAP) counterpart. MT1-MMP was observed
MT-MMPs in prostate cancer tissues. to be more strongly expressed in tumor tissue than in
PIN and NAP tissue, with the expression of MT1-MMP
Trudel et al. [17] examined tissues from 189 prostate reaching its highest levels in the most aggressive
cancer patients who had undergone surgery (radical prostate tumors with high Gleason scores (Gleason
prostatectomy). MT1-MMP expression and its scores are used to grade prostate cancer, with a score
effects on disease-free survival were examined above 7 indicative of aggressive, metastatic disease).
immunohistochemically, differentiating cancer, stromal, Once again, expression was detected in surrounding
and benign epithelial cells. This study showed that stroma and epithelia, backing up the findings of
[17]
in 167 (88.8%) cases, MT1-MMP was expressed by Trudel et al. . The authors speculate that stromal
benign epithelial cells and MT1-MMP was expressed and tumor cells could co-operate in facilitating tumor
by cancer cells in 171 (90.5%) cases. The expression cell invasion, hence the requirement for MT1-MMP
in cancerous tissue was mostly observed in cells at expression, and that transition from benign epithelium
or near the tumor front. Overall the expression was via PIN to cancer is associated with changes in
[20]
described as heterogeneous though cancer cells at the localisation of MT1-MMP in the prostate epithelium .
tumor margin were seen to always express MT1-MMP. [21]
The expression of MT1-MMP in benign epithelial cells In a further 40 patients, Reis et al. also monitored
was somewhat unexpected, given what is generally tissue inhibitor of matrix metalloproteinase 1 (TIMP-
understood about MMPs in other cancers. The authors 1) expression together with that of MT1-MMP. TIMPs
did raise the issue of the quality and specificity of inhibit some MMPs and other protease enzymes,
[22]
commercial antibodies for MT1-MMP, and did further but not MT1-MMP . The loss of TIMP-1 protein
expression was correlated to cancer progression,
suggest that active MT1-MMP could be cleaved by with MT1-MMP protein expression being identified
other MMPs resulting in soluble fragments, which may in the majority of prostate cancer specimens. Once
have been detected. It is the potential effect of prostate again, a positive correlation with Gleason score
cancer cells on the local microenvironment that is was observed [21] . This reinforced an earlier study
perhaps the key, however. The authors speculated by the same group (79 prostate cancer patients),
as to whether the presence of MT1-MMP in benign which indicated that MT1-MMP expression was
epithelial cells (near cancerous tissue) from these higher in patient samples with Gleason scores ≥ 7,
patients might in fact be induced by the cancer. A study though that dataset only exhibited marginal statistical
by Paterson et al. [18] in bladder cancer was cross- significance [23] .
referenced, which had further suggested that the so-
called “benign” epithelial cells in those patients were Upadhyay et al. [24] investigated the relationship
in fact not benign at all, but genotypically abnormal. between the MT1-MMP and MMP-2 expression,
These findings have been encountered by others and with immunohistochemistry confirmed by western
are worthy of further study. blotting and gelatin zymography. A significant
correlation between the pattern of MMP-2 and MT1-
Discrepancies between gene expression (higher MT1- MMP expression within the epithelial components
MMP expression in benign prostate hyperplasia and of individual specimens was observed. Differential
prostate cancer tissues, when compared to normal staining was seen between benign epithelia, high-
prostate) and protein expression (lower expression in grade PIN, and prostate cancer. In benign glands,
prostate cancer tissues compared to normal prostate the greatest expression for MT1-MMP was in basal
and benign prostate hyperplasia) were noted by cells (BCs), whereas secretory cells were rarely
Neuhaus et al. [19] . These results contrast with most positive. Conversely in high-grade PIN, secretory cells
other published studies, which led the authors to showed consistent cytoplasmic staining. In cancer
speculate that cells of the prostate interstitium (included cells, staining was heterogeneous and varied from no
in assessment of total immunofluorescence due to staining to very intense staining in select glands [24] .
MT1-MMP) may have increased protein expression
and may account for the apparent levels of protein High expression of insulin-like growth factor-1
expression seen in epithelial cells. receptor (IGF-1R) in prostate cancer was identified
by Sroka et al. [25] , who suggested that using MT1-
Cardillo et al. [20] analysed 38 paraffin-embedded MMP localization and IGF-1R expression may serve
samples from prostate cancer patients (who as a predictive biomarker of aggressive disease. MT1-
had undergone radical prostatectomy) by MMP expression was high in the apical regions of the
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ December 12, 2017 317