Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model

The Possible Role of Human Endogenous Retroviruses

Luca Ferrari, Marco Cafora, Federica Rota, Mirjam Hoxha, Simona Iodice, Letizia Tarantini, Maria Dolci, Serena Delbue, Anna Pistocchi, Valentina Bollati

Research output: Contribution to journalArticle

Abstract

Extracellular vesicles (EVs) are important components of the metastatic niche and are crucial in infiltration, metastasis, and immune tolerance processes during tumorigenesis. We hypothesized that human endogenous retroviruses (HERV) positive EVs derived from tumor cellsmay have a role in modulating the innate immune response. The study was conducted in two different colorectal cancer cell lines, representing different stages of cancer development: Caco-2, derived from a non-metastatic colorectal adenocarcinoma, and SK-CO-1, derived from metastatic colorectal adenocarcinoma (ascites). Both cell lines were treated with decitabine to induce global hypomethylation and to reactivate HERV expression. EVs were quantified by nanoparticle tracking analysis, and HERV-positive EV concentrations were measured by flow cytometry. The effect of EVs isolated from both untreated and decitabine-treated cells on the innate immune response was evaluated by injecting them in zebrafish embryos and then assessing Interleukin 1β (IL1-β), Interleukin 10 (IL-10), and the myeloperoxidase (mpx) expression levels by real-time qPCR. Interestingly, HERV-K positive EVs concentrations were significantly associated with a reduced expression of IL1-β and mpx, supporting our hypothesis that HERV-positive EVs may act as immunomodulators in tumor progression. The obtained results open new perspectives about the modulation of the immune response in cancer therapy.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number15
DOIs
Publication statusPublished - Jul 26 2019

Fingerprint

decitabine
interleukins
Endogenous Retroviruses
Zebrafish
cultured cells
Innate Immunity
Colorectal Neoplasms
cancer
Cells
Interleukin-1
Cell Line
Peroxidase
Tumors
tumors
cytometry
Flow cytometry
embryos
Immunologic Factors
metastasis
infiltration

Keywords

  • extracellular vesicles
  • HERV
  • innate immune response
  • zebrafish

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model : The Possible Role of Human Endogenous Retroviruses. / Ferrari, Luca; Cafora, Marco; Rota, Federica; Hoxha, Mirjam; Iodice, Simona; Tarantini, Letizia; Dolci, Maria; Delbue, Serena; Pistocchi, Anna; Bollati, Valentina.

In: International Journal of Molecular Sciences, Vol. 20, No. 15, 26.07.2019.

Research output: Contribution to journalArticle

Ferrari, Luca ; Cafora, Marco ; Rota, Federica ; Hoxha, Mirjam ; Iodice, Simona ; Tarantini, Letizia ; Dolci, Maria ; Delbue, Serena ; Pistocchi, Anna ; Bollati, Valentina. / Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model : The Possible Role of Human Endogenous Retroviruses. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 15.
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