MedicalResearch.com Interview with:
Armando E. del Río Hernández, PhD
European Research Council Fellow
Head, Cellular and Molecular Biomechanics Laboratory
Senior Lecturer, Department of Bioengineering
Imperial College London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Pancreatic cancer is an extremely aggressive disease with an unacceptably low survival rate that has not changed during the last 40 years despite significant efforts aimed at developing therapies against cancer cells.
Pancreatic cancer is characterised by an extensive desmoplasia, which forms the majority of the tissue around the tumour. This desmoplastic tissue is known to help the tumour to grow and metastasize, and hinders drug delivery.
We have focused our efforts on understanding how pancreatic stellate cells (PSCs), which are the key effectors that orchestrate the desmoplastic reaction in pancreatic cancer, can promote tumour progression. PSCs in healthy pancreas have abundant vitamin A storage in their cytoplasm and exist in a quiescent state that guarantees a balanced tissue homeostasis. In pancreatic cancer, loss of this balance activates PSCs, which lose the vitamin A content and remodel the surrounding tissue to make it favourable for cancer cell invasion.
We found that treating PSCs which ATRA (All trans-retinoic acid), the active metabolite of vitamin A mechanically reprograms PSCs to promote quiescence in vitro. Quiescent PSCs are unable to remodel the microenvironment to allow pancreatic cancer cell invasion.
To get more information about our findings please find the article in the open access journal Nature Communications:http://www.nature.com/articles/ncomms12630
MedicalResearch.com: What should readers take away from your report?
Response: The first thing we would like to highlight is that our study only looked at the behaviour of cells in the laboratory and we do not have evidence that patients would benefit from taking supplements of Vitamin A. Further testing is needed including clinical trials. However, these new insights into the mechanism by which vitamin A deactivates the cells responsible to create the desmoplastic reaction will open avenues to explore new possibilities for tackling the disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: As explained earlier, in the future new studies need to validate this mechanism using animal models, and also to investigate the effect of vitamin A to treat pancreatic cancer in clinical trials. It is possible that by deactivating the cells that promote this desmoplasia, vitamin A may contribute to increase the efficacy of chemotherapies to fight this tumour.
MedicalResearch.com: Is there anything else you would like to add?
Response: Today, treating pancreatic cancer is one of the most pressing clinical needs worldwide and there is an urgent requirement for new therapies. It is important then to approach this unsolved puzzle of pancreatic cancer combining concepts and technical tools available in the field of cancer and other disciplines such as biophysics, engineering, and mechanobiology.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Antonios Chronopoulos, Benjamin Robinson, Muge Sarper, Ernesto Cortes, Vera Auernheimer, Dariusz Lachowski, Simon Attwood, Rebeca García, Saba Ghassemi, Ben Fabry, Armando del Río Hernández. ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion. Nature Communications, 2016; 7: 12630 DOI: 10.1038/ncomms12630
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