Our latest article, published in Nature Communications. Read it here.
Pancreatic cancer is associated with advanced fibrosis, which is dense tissue that supports tumour growth, contributes to metastasis and hampers chemotherapy delivery. This fibrosis in pancreatic cancer is driven by pancreatic stellate cells (PSCs), which in this disease are activated and deficient in vitamin A as opposed to their healthy counterparts that reside in normal pancreas and have abundant droplets of vitamin A storage in their cytoplasm. Activated PSCs have a robust cytoskeleton which applies forces on the surrounding to stiffen the tissue and remodel the microenvironment of the tumour to make it favourable for cancer cell invasion.
Our research shows that restoring the vitamin A levels in these cells reprograms them to a quiescent stage similar to the one observed in healthy tissues. This suppresses actomyosin contraction, mechanosensing and force-mediated matrix remodelling and stiffening, which, in turn, creates a microenvironment unfavourable for invasion by pancreatic cancer cells. The reduced invasive behaviour of cancer cells was independent of paracrine signalling between PSCs and cancer cells, and was mostly attributed to the altered biomechanical and/or topographical characteristics of the remodelled microenvironment promoted by ATRA (vitamin A precursor)treatment on PSCs.