Ran Qi
Ran Qi, M.D., Tongji Hospital of Tongji University, China
Title: Cancer-associated Fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells though exosome derived ACSL4 -targeting miRNAS
Biography
Biography: Ran Qi
Abstract
Pancreatic cancer remains one of the deadliest cancer types in the world. Severe chemotherapy resistance leads to poor prognosis in patients with advanced pancreatic cancer, highlighting the need to investigate mechanisms and develop therapies to overcome chemoresistance.
Primary NFs and CAFs were collected from PDAC patient tumor samples and paracancerous pancreatic tissues. Exosomes were isolated by ultra-centrifugation and identified via western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and highâ€throughput sequencing. GEM was used to induce ferroptosis, and ferroptosis levels were evaluated via measuring lipid ROS, cell viability, and intracellular Fe2+ levels. A xenograft tumor model was used to evaluate in vivo tumor response.
Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, potentially through maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells.
The present study reveals a new mechanism of acquired chemo-resistance in PDAC and suggests this miR-3173-5p/ACSL4 pathway as a possible therapeutic target in Gem-resistant pancreatic cancer.