Vitamin A May Inhibit Pancreatic Cancer by Preventing Desmoplasia That Surrounds Tumor

MedicalResearch.com Interview with:

Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London

Dr. del Río Hernández

Armando E. del Río Hernández, PhD
European Research Council Fellow
Head, Cellular and Molecular Biomechanics Laboratory
http://biomechanicalregulation-lab.org/
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

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Protein Blocks Effects of Cancer Fighting Vitamin A Drug

Devanand Sarkar, M.B.B.S., Ph.D Harrison Scholar at VCU Massey Cancer Center, Blick Scholar and Associate Professor Department of Human and Molecular Genetics Member of the VCU Institute of Molecular Medicine Virginia Commonweath School of MedicineMedicalResearch.com Interview with:
Devanand Sarkar, M.B.B.S., Ph.D
Harrison Scholar at VCU Massey Cancer Center,
Blick Scholar and Associate Professor
Department of Human and Molecular Genetics
Member of the VCU Institute of Molecular Medicine
Virginia Commonweath School of Medicine

Medical Research: What are the main findings of the study?

Dr. Sarkar: Retinoic acid (Vitamin A) is an anti-cancer drug for a number of cancers including liver cancer. However, all patients do not respond to retinoic acid. Astrocyte elevated gene-1 (AEG-1) is overexpressed in a large percentage of cancer patients and promotes development and progression of cancer. In this study we document that AEG-1 inhibits retinoic acid function. Combinatorial strategy involving AEG-1 inhibition and retinoic acid synergistically blocks growth of human liver cancer cells in animal models.
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