scholarly journals Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model: The Possible Role of Human Endogenous Retroviruses

2019 ◽  
Vol 20 (15) ◽  
pp. 3669 ◽  
Author(s):  
Luca Ferrari ◽  
Marco Cafora ◽  
Federica Rota ◽  
Mirjam Hoxha ◽  
Simona Iodice ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Cell Lines ◽  
Cancer Cell ◽  
Innate Immune Response ◽  
Colorectal Adenocarcinoma ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Colorectal Cancer Cell Lines

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.

scholarly journals UHRF1 suppresses viral mimicry through both DNA methylation-dependent and -independent mechanisms

2020 ◽  
Author(s):  
RE Irwin ◽  
CA Scullion ◽  
SJ Thursby ◽  
ML Sun ◽  
A Thakur ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Cell Lines ◽  
Cancer Cell ◽  
Innate Immune Response ◽  
Point Mutations ◽  
Innate Immune ◽  
Lung Fibroblasts ◽  
Interferon Response ◽  
Viral Mimicry

AbstractSome chemotherapeutic agents which cause loss of DNA methylation have been recently shown to induce a state of “viral mimicry” involving upregulation of endogenous retroviruses (ERV) and a subsequent innate immune response. This approach may be useful in combination with immune checkpoint cancer therapies, but relatively little is known about normal cellular control of ERV suppression. The UHRF1 protein can interact with the maintenance methylation protein DNMT1 and is known to play an important role in epigenetic control in the cell. To examine potential roles of this protein in differentiated cells, we first established stable knockdowns in normal human lung fibroblasts. While these knockdown cells showed the expected loss of DNA methylation genome-wide, transcriptional changes were instead dominated by a single response, namely activation of innate immune signalling, consistent with viral mimicry. We confirmed using mechanistic approaches that activation of interferons and interferon-stimulated genes involved in double-stranded RNA detection was crucial to the response. ERVs were demethylated and transcriptionally activated in UHRF1 knockdown cells. As in these normal cell lines, ERV activation and interferon response also occurred following the transient loss of UHRF1 in both melanoma and colon cancer cell lines. Restoring UHRF1 in either transient- or stable knockdown systems abrogated ERV reactivation and interferon response, but without substantial restoration of DNA methylation. Rescued cell lines were hypersensitive to depletion of SETDB1, implicating H3K9me3 as crucial to UHRF1-mediated repression in the absence of DNA methylation. Confirming this, cells rescued with UHRF1 containing point mutations affecting H3K9me3 binding could not mediate silencing of ERV transcription or the innate immune response. Finally, by introducing similar point mutations in the mouse homologue, we could show that this pathway is conserved in mice. Our results therefore implicate UHRF1 as a key regulator of ERV suppression and strengthen the basis for cancer cell hypomethylation therapy.

scholarly journals Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 610 ◽  
Author(s):  
Vincent Alcazer ◽  
Paola Bonaventura ◽  
Stephane Depil
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Interferon Response ◽  
Human Endogenous Retroviruses ◽  
Dna Production ◽  
Potential Impact ◽  
Multiple Conditions

Human Endogenous Retroviruses (HERVs) are accounting for 8% of the human genome. These sequences are remnants from ancient germline infections by exogenous retroviruses. After million years of evolution and multiple integrations, HERVs have acquired many damages rendering them defective. At steady state, HERVs are mostly localized in the heterochromatin and silenced by methylation. Multiple conditions have been described to induce their reactivation, including auto-immune diseases and cancers. HERVs re-expression leads to RNA (simple and double-stranded) and DNA production (by reverse transcription), modulating the innate immune response. Some studies also argue for a role of HERVs in shaping the evolution of innate immunity, notably in the development of the interferon response. However, their exact role in the innate immune response, particularly in cancer, remains to be defined. In this review, we see how HERVs could be key-players in mounting an antitumor immune response. After a brief introduction on HERVs characteristics and biology, we review the different mechanisms by which HERVs can interact with the immune system, with a focus on the innate response. We then discuss the potential impact of HERVs expression on the innate immune response in cancer.

scholarly journals Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death

2021 ◽  
pp. 1-10
Author(s):  
Paulo Roberto Del Valle ◽  
Samir Andrade Mendonça ◽  
Fernanda Antunes ◽  
Aline Hunger ◽  
Rodrigo E Tamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Gene Transfer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Interferon Beta ◽  
Human Colorectal Cancer ◽  
Human Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines ◽  
Beta Gene

IGF2 knockdown in two colorectal cancer cell lines decreases survival, adhesion and modulates survival-associated genes

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 12485-12495 ◽  
Author(s):  
Michael A. Rogers ◽  
Verena Kalter ◽  
Moritz Strowitzki ◽  
Martin Schneider ◽  
Peter Lichter
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines

EXTL3/EXTR1 alterations in colorectal cancer cell lines.

1999 ◽  
Author(s):  
T Arai ◽  
Y Akiyama ◽  
H Nagasaki ◽  
N Murase ◽  
S Okabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Lines
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