| dc.description.abstract | Background. Colorectal cancer (CRC) has been one the most aggressive cancers, with
increasing prevalence worldwide. However, the pathophysiological molecular
mechanisms behind tumour development are still poorly characterized. An active
crosstalk between the intestinal epithelium and the underlying smooth muscle has been
recently demonstrated by our group, showing to be crucial for the regeneration of the
epithelium. In this process, the metalloproteinase MMP17 expressed mainly in the smooth
muscle plays an essential role. In addition, overexpression of PDGFRα in fibroblasts and
alterations in the synthesis of prostaglandin E2 have been linked to cancer. The aim of this
project is to study the epithelial-smooth muscle crosstalk in a tumorigenic background.
We assessed the bidirectionality of this crosstalk and the possible impact of MMP17's lack
on the smooth muscle characteristics in this tumoral scenario.
Results. The loss of Mmp17 in mice lead to higher number of PDGFRα+ cells in the
muscle, but no higher expression of the prostaglandin synthase mPGES1 in a WT
background. In addition, tumorigenic background leads to not only increase in the number
of PDGFRα+ cells in the muscle, but also higher expression of mPGES1 in the myenteric
plexus. In order to study the impact of tumoral epithelial cells on the smooth muscle
tissue, we developed an experimental model by collecting tumoral organoids supernatant
and exposing pinned smooth muscle to it.
Conclusions. This project allowed us to propose that Mmp17 has a crucial role in the
changes that occur in the smooth muscle of the small intestine in mice during tumour
development. Furthermore, data indicate a possible regulation of the smooth muscle by
the tumour intestinal epithelium. However, some results were inconclusive, and more
experiments are needed to assess the role of this crosstalk. | |
