---
title: "PDAC cells cross endothelium by filopodia-driven invasion or endothelial retraction"
id: "biorxiv-9-pancreatic-cancer-cells-breach-endothelial-barriers-through-protrusion-driven"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-9-pancreatic-cancer-cells-breach-endothelial-barriers-through-protrusion-driven"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.02.749041v1?rss=1"
published_at: "2026-09-03T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PDAC cells cross endothelium by filopodia-driven invasion or endothelial retraction
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-9-pancreatic-cancer-cells-breach-endothelial-barriers-through-protrusion-driven
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.02.749041v1?rss=1)
- **Published At:** 2026-09-03T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- This preprint reports that **pancreatic ductal adenocarcinoma (PDAC)** cells extravasate from blood vessels by two distinct mechanisms: a protrusion-driven invasion and an endothelial retraction–mediated route. - MIA PaCa-2 cells breach endothelial junctions using **filopodia-like protrusions**, allowing direct access to and dissemination across the basal extracellular matrix (ECM). - AsPC-1 cells remain rounded on the endothelial surface and provoke rapid **endothelial retraction**, leading to detachment of endothelial cells from the basal lamina and tumor cell crossing without obvious protrusive invasion. - The retraction mechanism is associated with AsPC-1–secreted factors that destabilize endothelial monolayers and with induction of **endothelial apoptosis**; however, inhibition of apoptosis alone does not prevent barrier disruption. - Both extravasation modes were observed in zebrafish larvae, and in the mouse lung AsPC-1 cells arrest, survive, induce endothelial detachment, and extravasate via the retraction mechanism before metastatic growth. - Pharmacologic blockade with the Src-family kinase inhibitor **saracatinib** preserves endothelial barrier integrity, reduces early vascular disruption in the lung, and delays metastatic outgrowth in the models reported. - The findings indicate that PDAC cells can use mechanistically distinct routes to cross endothelial barriers and suggest that effective anti-metastatic strategies may need to target multiple modes of barrier breach rather than a single pathway. - Competing interests: one author (L.M.C.) has consultancy and mentorship roles unrelated to this work; other authors declared no competing or financial interests. Funding sources and institutional affiliations are reported in the preprint.
## Clinical Analysis & Structured Key Points
Pancreatic cancer cells breach endothelial barriers through protrusion-driven invasion or endothelial retraction | bioRxiv Skip to main content New Results Pancreatic cancer cells breach endothelial barriers through protrusion-driven invasion or endothelial retraction View ORCID Profile Gautier Follain , View ORCID Profile Sujan Ghimire , View ORCID Profile Monika Vaitkevičiūtė , Helene Helo , View ORCID Profile Joanna W. Pylvänäinen , View ORCID Profile Frédéric Fercoq , View ORCID Profile Aleksi Isomursu , View ORCID Profile Megan R. Chastney , View ORCID Profile Omkar Joshi , Marco De Donatis , View ORCID Profile Ermei Mäkilä , View ORCID Profile James R.W. Conway , View ORCID Profile Marko Salmi , View ORCID Profile Sara A. Wickström , View ORCID Profile Leo M. Carlin , View ORCID Profile Johanna Ivaska , View ORCID Profile Guillaume Jacquemet doi: https://doi.org/10.64898/2026.09.02.749041 Gautier Follain 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gautier Follain Sujan Ghimire 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sujan Ghimire Monika Vaitkevičiūtė 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Monika Vaitkevičiūtė Helene Helo 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joanna W. Pylvänäinen 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joanna W. Pylvänäinen Frédéric Fercoq 2 Cancer Research UK Scotland Institute, Garscube Estate, Glasgow G61 1BD, United Kingdom.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Frédéric Fercoq Aleksi Isomursu 3 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Aleksi Isomursu Megan R. Chastney 3 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Megan R. Chastney Omkar Joshi 3 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Omkar Joshi Marco De Donatis 4 Cancer Research UK Scotland Institute, Garscube Estate, Glasgow G61 1BD, United Kingdom.; School of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ermei Mäkilä 5 Laboratory of Industrial Physics, Department of Physics and Astronomy, Faculty of Science, University of Turku, Vesilinnantie 5, FI-20500 Turku, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ermei Mäkilä James R.W. Conway 6 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Turku Collegium for Science, Medicine and Technology (TCSMT), University of Turku, FI-20520 Turku, Finland.; Faculty of Medicine and Health Technology, T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for James R.W. Conway Marko Salmi 7 InFLAMES Research Flagship Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marko Salmi Sara A. Wickström 8 Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sara A. Wickström Leo M. Carlin 4 Cancer Research UK Scotland Institute, Garscube Estate, Glasgow G61 1BD, United Kingdom.; School of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Leo M. Carlin Johanna Ivaska 9 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Department of Life Technologies, Universi Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Johanna Ivaska Guillaume Jacquemet 1 Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.; InFLAMES Research Flagship Center, University of T; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Guillaume Jacquemet For correspondence: guillaume.jacquemet{at}abo.fi Abstract Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Extravasation, the exit of circulating cancer cells from blood vessels, is a critical yet poorly understood step in metastatic dissemination. Here we show that pancreatic ductal adenocarcinoma (PDAC) cells can breach endothelial barriers through two mechanistically distinct modes of extravasation. MIA PaCa-2 cells breach endothelial junctions via filopodia-like protrusions, enabling access to and spread across the basal extracellular matrix (ECM). By contrast, AsPC-1 cells remain rounded atop the endothelium and cross the barrier by triggering rapid retraction of neighbouring endothelial cells. These distinct extravasation modes were also observed in zebrafish larvae. In the mouse lung, AsPC-1 cells arrest, survive, induce endothelial detachment from the basal lamina, and extravasate through this retraction mechanism before metastatic outgrowth. Mechanistically, AsPC-1-secreted factors are sufficient to destabilise endothelial monolayers, and AsPC-1 cells also induce endothelial apoptosis; however, blocking apoptosis does not prevent barrier disruption. By contrast, treatment with saracatinib, a Src-family kinase inhibitor, protects endothelial barriers, limits early vascular disruption in the lung, and delays metastatic outgrowth. Together, these findings reveal that PDAC cells can extravasate via mechanistically distinct routes, suggesting that effective anti-metastatic strategies may need to target multiple modes of endothelial barrier breach rather than a single pathway. Competing Interest Statement L.M.C. has consulted for Ono Pharmaceuticals UK and is an academic mentor to a team at BioMedX Heidelberg on work unrelated to this article. The other authors declare no competing or financial interests. Footnotes https://zenodo.org/records/22228666 Funder Information Declared Research Council of Finland, https://ror.org/05k73zm37 , 338537 , 371287 , 374180 , 360775 , 332402 , 346131 Research Council of Finland , 359073 , 358879 , 367582 , 367577 Sigrid Jusélius Foundation, https://ror.org/00ckakm23 Cancer Foundation Finland (Syöpäjärjestöt) Jane and Aatos Erkko Foundation, https://ror.org/03vxy9y38 Finnish Cancer Institute Cancer Research UK Scotland Institute , A23983 , A31287 CRUK Scotland Centre , CTRQQR-2021\100006 Breast Cancer Now , 2019DecPR1424 Max Planck Society, https://ror.org/01hhn8329 European Research Council , 101142305 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Posted September 03, 2026. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Pancreatic cancer cells breach endothelial barriers through protrusion-driven invasion or endothelial retraction Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Pancreatic cancer cells breach endothelial barriers through protrusion-driven invasion or endothelial retraction Gautier Follain , Sujan Ghimire , Monika Vaitkevičiūtė , Helene Helo , Joanna W. Pylvänäinen , Frédéric Fercoq , Aleksi Isomursu , Megan R. Chastney , Omkar Joshi , Marco De Donatis , Ermei Mäkilä , James R.W. Conway , Marko Salmi , Sara A. Wickström , Leo M. Carlin , Johanna Ivaska , Guillaume Jacquemet bioRxiv 2026.09.02.749041; doi: https://doi.org/10.64898/2026.09.02.749041 Share This Article: Copy Citation Tools Pancreatic cancer cells breach endothelial barriers through protrusion-driven invasion or endothelial retraction Gautier Follain , Sujan Ghimire , Monika Vaitkevičiūtė , Helene Helo , Joanna W. Pylvänäinen , Frédéric Fercoq , Aleksi Isomursu , Megan R. Chastney , Omkar Joshi , Marco De Donatis , Ermei Mäkilä , James R.W. Conway , Marko Salmi , Sara A. Wickström , Leo M. Carlin , Johanna Ivaska , Guillaume Jacquemet bioRxiv 2026.09.02.749041; doi: https://doi.org/10.64898/2026.09.02.749041 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7957) Biochemistry (18606) Bioengineering (14747) Bioinformatics (44062) Biophysics (22432) Cancer Biology (19561) Cell Biology (26713) Clinical Trials (138) Developmental Biology (13880) Ecology (20848) Epidemiology (2067) Evolutionary Biology (25272) Genetics (16086) Genomics (23370) Immunology (18563) Microbiology (42166) Molecular Biology (17929) Neuroscience (92715) Paleontology (693) Pathology (2964) Pharmacology and Toxicology (5054) Physiology (8043) Plant Biology (15887) Scientific Communication and Education (2090) Synthetic Biology (4533) Systems Biology (10170) Zoology (2371)
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