A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Fast label-free live imaging with FlowVision reveals key principles of cancer cell arrest on endothelial monolayers
Tekijät: Follain, Gautier; Ghimire, Sujan; Pylvänäinen, Joanna W; Vaitkevičiūtė, Monika; Hidalgo-Cenalmor, Iván; Wurzinger, Diana; Guzmán, Camilo; Conway, James R W; Dibus, Michal; Härkönen, Jouni; Oikari, Sanna; Rilla, Kirsi; Salmi, Marko; Ivaska, Johanna; Jacquemet, Guillaume
Kustantaja: Springer Science and Business Media LLC
Julkaisuvuosi: 2026
Lehti: EMBO Journal
Vuosikerta: 45
Numero: 4
Aloitussivu: 1381
Lopetussivu: 1421
ISSN: 0261-4189
eISSN: 1460-2075
DOI: https://doi.org/10.1038/s44318-025-00678-9
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1038/s44318-025-00678-9
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/508358619
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
The rapid, transient, and unpredictable nature of interactions between circulating cells and the endothelium challenges the investigation of these events under flow conditions. Here, we developed an imaging and image-analysis framework called FlowVision, which integrates fast, bright-field live-cell imaging with deep-learning-based image analysis to quantitatively track cell landing and arrest on an endothelial monolayer under physiological flow conditions. Using FlowVision, we find that pancreatic ductal adenocarcinoma (PDAC) cells exhibit variable adhesion strength and flow sensitivity. Remarkably, some PDAC cells demonstrate comparable endothelial engagement to leukocytes, preferentially arresting at endothelial junctions, providing them access to the underlying basal extracellular matrix. PDAC cells attach and form clusters in areas with high expression of the endothelial CD44 receptor. Targeting CD44 using siRNA, function-blocking antibodies, or degrading its ligand, hyaluronic acid (HA), strongly reduces PDAC cell attachment. Overall, our label-free live-imaging approach demonstrates that cancer and immune cells share both common and unique features in endothelial adhesion under flow, and allows identification of CD44 and HA as key mediators of PDAC cell arrest.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This study was supported by the Research Council of Finland (338537 and 371287 to GJ; 325464 to JI; 338585 and 360775 to JRWC, and 332402 to GF), the Sigrid Juselius Foundation (to GJ and to JI), the Cancer Society of Finland (Syöpäjärjestöt; to GJ, MS, and JI), and the Solutions for Health strategic funding to Åbo Akademi University (to GJ). This research was supported by the InFLAMES and GeneCellNano Flagships Programme of the Research Council of Finland (decision numbers: 337530, 337531, 357910, 35791, and 337120). This work was also supported by the Finnish Cancer Institute (K. Albin Johansson Professorship, JI), the Research Council of Finland Centre of Excellence program (346131 & 364182 to JI), and the Jane and Aatos Erkko Foundation (JI). JRWC and MD were supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement (841973 and 101108089). The Turku Collegium for Science, Medicine, and Technologies supported GF. The authors acknowledge Euro-BioImaging ERIC (https://ror.org/05d78xc36) for providing access to imaging technologies and services via the Finnish Advanced Microscopy Node (FiAM) in Turku, Finland (https://ror.org/023f5cj14). The Cell Imaging and Cytometry Core facility, the Zebrafish Core (both at Turku Bioscience, University of Turku, Åbo Akademi University, and supported by Biocenter Finland), Turku Bioimaging and the Genome Biology Unit (Research Programs Unit, HiLIFE Helsinki Institute of Life Science, Faculty of Medicine, University of Helsinki, Biocenter Finland) are acknowledged for services, instrumentation, and expertise. We thank Hamidi H and Harlepp S for critical reading of the manuscript. We also thank Laasola P. for blood isolation and preparation, and express our gratitude to the anonymous blood donors for their contributions to this study.
