Page 104 - Read Online

Spencer et al. J Cancer Metastasis Treat 2022;8:2 https://dx.doi.org/10.20517/2394-4722.2021.174 Page 3 of 15

Figure 1. Expression of MT1-MMP in Sarcoma. (A) MMP-14 (the gene for MT1-MMP) expression in various cancer types
[6]
(www.cbioportal.org/) [4,5] . (B) MMP-14 expression in various types of sarcoma (http://ist.medisapiens.com/) . (Figure adapted from
[7]
Figure 1 in Ref 7 ).
MT1-MMP and MMP-2, which was also shown to correlate with poorer prognosis. In a follow-up study, it
was found that the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), a substrate of
MT1-MMP which aids in MMP stimulation, and the co-expression of EMMPRIN and MT1-MMP were
predictors of poor prognosis .
[13]

In another study, the expression of MMPs and their endogenous inhibitors were investigated in 11 tumour
xenografts and 12 OS biopsies (6 from primary tumours and 6 from metastases) . MMP-14 mRNA, along
[14]
with MMP-2, TIMP-1 and TIMP-2 mRNA, was identified in the majority of samples, with a consistent
pattern of expression of MMP-14, MMP-2 and TIMP-2 in both the xenografts and biopsies. The authors
stated that a pattern of MMP and TIMP expression in metastases, when compared with primary tumours,
could not be discerned.

[15]
Utilising high-throughput sequencing, Xiao et al. screened for 339 genes known to be associated with
cancer progression in 10 samples from OS patients from China. It was shown that the 10 samples tested
demonstrated on average more than 200 gene mutations, including the MMP-14 gene. Although the
findings from this study are in line with previously published studies , a more comprehensive evaluation
[16]
of the OS genome in larger collections of OS samples is required to identify high-yield mutations.

Whole transcriptosome analysis was performed on 33 OS patient samples. Tumour and normal tissues were
collected from 18 bone samples following resection and 15 formalin-fixed paraffin-embedded (FFPE)
samples that were retrieved from pathology archives. The genes that were most significantly downregulated
[17]
and upregulated in the tumour tissues were identified . MMP-14 was shown to be the 7th most
upregulated gene in osteosarcoma, with a greater than 2-fold increase in gene expression in 87% of tumour
samples when compared to their matched controls. Of these, 47% also showed elevated levels of MMP-2
and/or MMP-9. Enrichment analysis showed that there were significant alterations in the genes shown to
regulate collagen degradation, extracellular matrix (ECM) organisation and ECM degradation, including
collagens; COL11A1, COL2A1 and COL10A1; among others. In the FFPE samples, it was evident that
chemotherapy had not brought about any significant changes in MMP-14, MMP-2 and MMP-9 expression.