Transcriptomic analysis of MMP8 effects on murine mammary carcinoma progression

Berg, Hege (2016) Transcriptomic analysis of MMP8 effects on murine mammary carcinoma progression. Masters thesis, University of East Anglia.

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It is well established that Matrix metalloproteinase-8 (MMP8) suppresses
growth and metastasis of tumours, and accumulating data suggest that this
protective effect is propagated via the immune system. Recent reports links
MMP8 to TGFb signaling, which is known to induce polarization of neutrophils
and macrophages towards their pro-tumorigenic phenotypes; N2 and M2.
However, the role of MMP8 as a regulator of the TGFb mediated polarization of
myeloid cells is unexplored. The present study analysed the transcriptome of
tumours from MMTV-PyMT mice, intercrossed with Mmp8-null mice, to explore
whether depletion of MMP8 affects myeloid cell polarisation and, to investigate
novel pathways affected by MMP8 signaling. Results from qRT-PCR suggests an
increased infiltration of both anti- and pro-tumorigenic myeloid cells at later
time points, however, these results were not confirmed by RNAseq analysis. In
contrast to these results, analysis of the whole transcriptome of MMTV-PyMT
tumours showed that depletion of MMP8 induces an up-regulation of gene sets
specific for B- and T-lymphocytes and, lipid and glycerol metabolism at 6 and
10 weeks, respectively, as well as inducing a disturbance in the web of
proteases. Additionally, several oncogenic proteins showed increased
expression in Mmp8-null mice. Although further validation is required to
confirm the current findings, these results suggest a complex role of MMP8
during tumour progression, in which pleiotropic changes are observed in
response to MMP8 ablation. These findings should be further explored in future
studies to achieve a better understanding of the mechanistic actions of MMP8,
which, in turn, could provide important implications for treatment of breast
cancer patients.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 4971 not found.
Date Deposited: 21 Jul 2017 12:37
Last Modified: 21 Jul 2017 12:37


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