Periodic Reporting for period 3 - MATRICAN (Matrix during cancer progression)
Reporting period: 2019-09-01 to 2021-02-28
We have developed a method to isolate ECM scaffolds from organs and tumours such that the 3 dimensional architecture is preserved. We can analyse these ECM scaffolds to know what components they are comprised of and to visualise their structure. The aim of the project is to analyse ECM scaffolds isolated from healthy and cancer-bearing organs to identify potential opportunities for therapeutic intervention to block cancer progression. The overall objectives are to characterise how the ECM scaffold is altered between healthy and cancer states, to test new therapeutic targeting strategies and to study the underlying biology to know how the ECM scaffold can control cell behaviour.
This project is important to society because it studies fundamental biology providing new information on how the body function and how cancer is regulated, and also by developing new therapeutic strategies to block cancer progression that could be translated into the clinic to decrease cancer patient suffering and increase cancer patient survival.
We had previously collected information on ECM scaffolds from a very basic model of breast cancer. We identified several targets to investigate and have found that these indeed do play a major role in regulating cancer progression. We are finalising four manuscripts to publish these findings. We have now collected ECM scaffolds from a more complex model of cancer that more closely recapitulate human disease. We have analysed these samples by mass spectrometry and are currently selecting which targets to follow up.
In parallel, we have investigated signalling in pancreatic cancer tumours and identified a kinase inhibitor effective against tumour progression. This study was submitted and is currently under revision.
Given the low throughput nature of the bioreactor studies and the challenges with acquiring quantitative data, we have developed in we have developed in vitro methods to study cell response to ECM proteins. These studies are ongoing.