Journal article
Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma
Cancers, Vol.13(11), 2727
05/31/2021
DOI: 10.3390/cancers13112727
PMID: 34072942
Abstract
Simple Summary
Circulating tumor cells (CTCs) found in the blood of pancreatic cancer patients show a worse prognosis to therapy if they are seen in clusters of cells with neutrophils or platelets or with other cell types than when they are seen as singlets. We wanted to investigate if there is a secondary mode of communication between the CTCs and neutrophils that causes them to associate. We describe for the first time an extravesicular (EV) mediated communication between CTCs and neutrophils that modulates early transcriptome changes that can cause neutrophils to partially degranulate and form associations. We also identify the protein cargo carried in such EVs and how when added to naive neutrophils, they can modulate transcriptomic changes in neutrophils partially disarming them to form clusters rather than undergo specialized cell death, which is characterized by release of condensed chromatin (NETs) and granular contents termed as NETosis.
Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell-cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tissue plasminogen activator and other proteins that can regulate cluster formation. By exposing naive neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on companion cells in clusters.
Details
- Title: Subtitle
- Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma
- Creators
- Harrys Kishore Charles Jacob - University of MiamiJohn Lalith Charles Richard - VIT Bhopal UniversityRossana Signorelli - University of MiamiTyler Kashuv - University of MiamiShweta Lavania - University of MiamiUtpreksha Vaish - University of Alabama at BirminghamRanjitha Boopathy - Shiv Nadar UniversityAshley Middleton - University of MiamiMelinda Minucci Boone - University of MiamiRamakrishnan Sundaram - University of MiamiVikas Dudeja - University of MiamiAshok Kumar Saluja - University of Miami
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.13(11), 2727
- DOI
- 10.3390/cancers13112727
- PMID
- 34072942
- NLM abbreviation
- Cancers (Basel)
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Publisher
- Mdpi
- Number of pages
- 25
- Grant note
- NIH 5RO1CA124723 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Sylvester Comprehensive Cancer Center, University of Miami Health System
- Language
- English
- Date published
- 05/31/2021
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244572602771
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