Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Systemic coagulopathy drives host lethality in a new Drosophila tumor model

View ORCID ProfileTsai-Ching Hsi, View ORCID ProfileKaty L Ong, View ORCID ProfileJorian J Sepers, View ORCID ProfileJung Kim, View ORCID ProfileDavid Bilder
doi: https://doi.org/10.1101/2022.05.11.491522
Tsai-Ching Hsi
1Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley CA, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tsai-Ching Hsi
Katy L Ong
1Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley CA, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Katy L Ong
Jorian J Sepers
1Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley CA, 94720, USA
2Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jorian J Sepers
Jung Kim
1Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley CA, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jung Kim
David Bilder
1Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley CA, 94720, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Bilder
  • For correspondence: bilder@berkeley.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Malignant tumors trigger a complex network of inflammatory and wound repair responses, prompting Dvorak's characterization of tumors as 'wounds that never heal'. Some of these responses lead to profound defects in blood clotting, such as Disseminated Intravascular Coagulopathy (DIC), which correlate with poor prognoses. Here, we demonstrate that a new tumor model in Drosophila provokes phenotypes that recapitulate coagulopathies observed in patients. Fly ovarian tumors overproduce multiple secreted components of the clotting cascade and trigger hypercoagulation of fly blood (hemolymph). Hypercoagulation occurs shortly after tumor induction and is transient; it is followed by a hypocoagulative state that is defective in wound healing. Cellular clotting regulators accumulate on the tumor over time and are depleted from the body, suggesting that hypocoagulation is caused by malignant growth exhaustion of host clotting components. Interestingly, clinical studies have suggested that lethality in patients with high serum levels of clotting components can be independent of thrombotic events. We show that rescuing coagulopathy improves survival of tumor-bearing flies, despite the fact that flies have an open circulatory system. Our work establishes a platform for identifying alternative mechanisms by which tumor-driven coagulopathy triggers early mortality, as well as exploring other conserved mechanisms of host responses to chronic wounds.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 11, 2022.
Download PDF
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.

Enter multiple addresses on separate lines or separate them with commas.
Systemic coagulopathy drives host lethality in a new Drosophila tumor model
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Systemic coagulopathy drives host lethality in a new Drosophila tumor model
Tsai-Ching Hsi, Katy L Ong, Jorian J Sepers, Jung Kim, David Bilder
bioRxiv 2022.05.11.491522; doi: https://doi.org/10.1101/2022.05.11.491522
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Systemic coagulopathy drives host lethality in a new Drosophila tumor model
Tsai-Ching Hsi, Katy L Ong, Jorian J Sepers, Jung Kim, David Bilder
bioRxiv 2022.05.11.491522; doi: https://doi.org/10.1101/2022.05.11.491522

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 Area

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3514)
  • Biochemistry (7365)
  • Bioengineering (5342)
  • Bioinformatics (20318)
  • Biophysics (10041)
  • Cancer Biology (7773)
  • Cell Biology (11348)
  • Clinical Trials (138)
  • Developmental Biology (6450)
  • Ecology (9979)
  • Epidemiology (2065)
  • Evolutionary Biology (13354)
  • Genetics (9370)
  • Genomics (12607)
  • Immunology (7724)
  • Microbiology (19087)
  • Molecular Biology (7459)
  • Neuroscience (41134)
  • Paleontology (300)
  • Pathology (1235)
  • Pharmacology and Toxicology (2142)
  • Physiology (3177)
  • Plant Biology (6878)
  • Scientific Communication and Education (1276)
  • Synthetic Biology (1900)
  • Systems Biology (5328)
  • Zoology (1091)