Modulation of early neutrophil granulation: The circulating tumor cell‐extravesicular connection in pancreatic ductal adenocarcinoma

Harrys Kishore Charles Jacob, John Lalith Charles Richard, Rossana Signorelli, Tyler Kashuv, Shweta Lavania, Utpreksha Vaish, Ranjitha Boopathy, Ashley Middleton, Melinda Minucci Boone, Ramakrishnan Sundaram, Vikas Dudeja, Ashok Kumar Saluja

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor cells dissociate from the primary site and enter into systemic circulation (circulat-ing 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 neutro-phils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modu-late degranulation and granule mobilization in neutrophils and, also, contain tissue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve 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.

Original languageEnglish (US)
Article number2727
JournalCancers
Volume13
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • Circulating tumor cells
  • Clusters
  • Extracellular vesicles
  • Granule mobiliza-tion
  • Neutrophil degranulation
  • Pancreatic cancer
  • Reteplase activity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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