Interferon-stimulated gene 15 modulates cell migration by interacting with Rac1 and contributes to lymph node metastasis of oral squamous cell carcinoma cells

Chen, Yulin; Wu, Wei; Jang, Chuan-Wei; Yen, Yi-Chen; Wang, Ssu-Han; Tsai, Fang‐Yu; Shen, Yingying; Chen, Yawen

doi:10.1038/s41388-019-0731-8

Cited by 29 publications

(20 citation statements)

References 58 publications

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“…Gene expression profiling demonstrated that expression of ISG15 DGG in the epidermis stimulated the migration of innate immune cells and endothelial cells, as well as extracellular matrix degradation and remodeling. Endogenous ISG15 has been implicated in migration of different cancer cell lines (43). Furthermore, recombinant ISG15 was found to induce neutrophil chemotaxis in vitro (44) and influx of DCs to the site of infection in vivo (34).…”

Section: Discussionmentioning

confidence: 99%

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

Iglesias-Guimarais

Ahrends

Vries

et al. 2020

The Journal of Immunology

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Type I IFN is produced upon infection and tissue damage and induces the expression of many IFN-stimulated genes (ISGs) that encode host-protective proteins. ISG15 is a ubiquitin-like molecule that can be conjugated to proteins but is also released from cells in a free form. Free, extracellular ISG15 is suggested to have an immune-regulatory role, based on disease phenotypes of ISG15-deficient humans and mice. However, the underlying mechanisms by which free ISG15 would act as a “cytokine” are unclear and much debated. We, in this study, demonstrate in a clinically relevant mouse model of therapeutic vaccination that free ISG15 is an alarmin that induces tissue alert, characterized by extracellular matrix remodeling, myeloid cell infiltration, and inflammation. Moreover, free ISG15 is a potent adjuvant for the CTL response. ISG15 produced at the vaccination site promoted the vaccine-specific CTL response by enhancing expansion, short-lived effector and effector/memory differentiation of CD8+ T cells. The function of free ISG15 as an extracellular ligand was demonstrated, because the equivalents in murine ISG15 of 2 aa recently implicated in binding of human ISG15 to LFA-1 in vitro were required for its adjuvant effect in vivo. Moreover, in further agreement with the in vitro findings on human cells, free ISG15 boosted the CTL response in vivo via NK cells in the absence of CD4+ T cell help. Thus, free ISG15 is part of a newly recognized innate route to promote the CTL response.

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Section: Discussionmentioning

confidence: 99%

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

Iglesias-Guimarais

Ahrends

Vries

et al. 2020

The Journal of Immunology

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“…[7][8][9][10] Moreover, metabonomics have also a strong ability to recognize cancer metastases. [11][12][13]…”

Section: Discussionmentioning

confidence: 99%

<p>Study of the Relationship Between Serum Amino Acid Metabolism and Lymph Node Metastasis in Patients with Colorectal Cancer</p>

Liu¹,

Wang²,

Ma³

et al. 2020

OTT

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Purpose: Lymph node metastasis is one of the important prognostic factors of colorectal cancer, and an important index of individualized treatment. The purpose of this study is to use metabonomics to identify potential molecular markers of lymph node metastasis in colorectal cancer (CRC). Patients and Methods: Peripheral blood samples of 223 CRC patients were collected. The metabolic levels of amino acids and carnitine in peripheral blood of CRC patients, with and without lymph node metastasis, were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The results show that there were significant differences in the levels of serum amino acids and carnitine between lymph node metastatic patients and lymph node nonmetastatic patients. The diagnostic model that was constructed by 9 types of serum metabolites has a high diagnostic ability. Conclusion: LC-MS/MS is a detection method that has a broad application in predicting CRC prognosis, individualized treatment, and in studying the mechanism of lymph node metastasis.

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“…Spheroids were formed as described previously [56] and then examined under a bright-field microscope. The size and diameter of tumor sphere were quantitatively measured by ImageJ (National Institutes of Health, Bethesda, MD, USA).…”

Section: Sphere Formation Assaymentioning

confidence: 99%

ERK Activation Modulates Cancer Stemness and Motility of a Novel Mouse Oral Squamous Cell Carcinoma Cell Line

Chen

Liu

Jang

et al. 2019

Cancers

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We established the NHRI-HN1 cell line from a mouse tongue tumor induced by 4-nitroquinoline 1-oxide (4-NQO)/arecoline, with further selection for cell stemness via in vitro sphere culture, to evaluate potential immunotherapies for oral squamous cell carcinoma (OSCC) in East and Southeast Asia. In vivo and in vitro phenotypic characterization, including tumor growth, immune modulator administration, gene expression, morphology, migration, invasion, and sphere formation assays, were conducted. NHRI-HN1 cells are capable of generating orthotopic tumors in syngeneic mice. Interestingly, immune stimulation via CpG oligodeoxynucleotide (CpG-ODN) dramatically reduced the tumor growth in NHRI-HN1 cell-injected syngeneic mice. The pathways enriched in genes that were differentially expressed in NHRI-HN1 cells when compared to non-tumorigenic cells were similar to those that were identified when comparing human OSCC and non-tumorous tissues. NHRI-HN1 cells have characteristics of epithelial–mesenchymal transition (EMT), including enhanced migration and invasion. NHRI-HN1 cells showed aggressive cell growth and sphere formation. The blockage of extracellular signal-regulated kinase (ERK) activation suppressed cell migration and reduced stemness characteristics in NHRI-HN1 cells, similar to human OSCC cell lines. Our data suggest that NHRI-HN1 cells, showing tumorigenic characteristics of EMT, cancer stemness, and ERK activation, are sufficient in modeling human OSCC and also competent for use in investigating oral cancer immunotherapies.

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Interferon-stimulated gene 15 modulates cell migration by interacting with Rac1 and contributes to lymph node metastasis of oral squamous cell carcinoma cells

Cited by 29 publications

References 58 publications

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

<p>Study of the Relationship Between Serum Amino Acid Metabolism and Lymph Node Metastasis in Patients with Colorectal Cancer</p>

ERK Activation Modulates Cancer Stemness and Motility of a Novel Mouse Oral Squamous Cell Carcinoma Cell Line

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