Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status
Wang Yingxiao; Samuel Michael S.; Ritchie Shona; Warren Sean C.; Yin Julia X.; Metcalf Xanthe L.; Murphy Kendelle J.; Magenau Astrid; Da Silva Andrew; Major Gretel; Grimmond Sean M.; Samra Jaswinder; Gadegaard Nikolaj; Chambers Cecilia R.; Abdulkhalek Lea; Lyons J. Guy; Goetz Jacky G.; Vennin Claire; Nobis Max; Caldon C. Elizabeth; Chou Angela; Zaratzian Anaiis; Parkin Ashleigh; Herrmann David; Tayao Michael; Stoehr Janett; Timpson Paul; Biankin Andrew V; Reed Daniel A.; Cox Thomas R.; Lee Victoria; Skhinas Joanna N.; Daly Roger J.; Gill Anthony J.; Conway James R. W.; Sansom Owen J.; Morton Jennifer P.; Burgess Andrew; Lucas Morghan C.; Trpceski Michael; Horvath Lisa G.; Bidanel Romain; Pajic Marina; Lyons Ruth J.; Pereira Brooke A.; Johns Amber L.; Filipe Elysse C.
Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status
Wang Yingxiao
Samuel Michael S.
Ritchie Shona
Warren Sean C.
Yin Julia X.
Metcalf Xanthe L.
Murphy Kendelle J.
Magenau Astrid
Da Silva Andrew
Major Gretel
Grimmond Sean M.
Samra Jaswinder
Gadegaard Nikolaj
Chambers Cecilia R.
Abdulkhalek Lea
Lyons J. Guy
Goetz Jacky G.
Vennin Claire
Nobis Max
Caldon C. Elizabeth
Chou Angela
Zaratzian Anaiis
Parkin Ashleigh
Herrmann David
Tayao Michael
Stoehr Janett
Timpson Paul
Biankin Andrew V
Reed Daniel A.
Cox Thomas R.
Lee Victoria
Skhinas Joanna N.
Daly Roger J.
Gill Anthony J.
Conway James R. W.
Sansom Owen J.
Morton Jennifer P.
Burgess Andrew
Lucas Morghan C.
Trpceski Michael
Horvath Lisa G.
Bidanel Romain
Pajic Marina
Lyons Ruth J.
Pereira Brooke A.
Johns Amber L.
Filipe Elysse C.
AMER ASSOC ADVANCEMENT SCIENCE
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021120158531
https://urn.fi/URN:NBN:fi-fe2021120158531
Tiivistelmä
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic, chemoresistant malignancy and is characterized by a dense, desmoplastic stroma that modulates PDAC progression. Here, we visualized transient manipulation of focal adhesion kinase (FAK), which integrates bidirectional cell-environment signaling, using intravital fluorescence lifetime imaging microscopy of the FAK-based Forster resonance energy transfer biosensor in mouse and patient-derived PDAC models. Parallel real-time quantification of the FUCCI cell cycle reporter guided us to improve PDAC response to standard-of-care chemotherapy at primary and secondary sites. Critically, micro-patterned pillar plates and stiffness-tunable matrices were used to pinpoint the contribution of environmental cues to chemosensitization, while fluid flow-induced shear stress assessment, patient-derived matrices, and personalized in vivo models allowed us to deconstruct how FAK inhibition can reduce PDAC spread. Last, stratification of PDAC patient samples via Merlin status revealed a patient subset with poor prognosis that are likely to respond to FAK priming before chemotherapy.
Kokoelmat
- Rinnakkaistallenteet [19207]