Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs

AbstractExtracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

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THE COMPARISON OF THE EFFECTS OF PANOBINOSTAT AND PKF118-310 ON β-CATENIN-DEPENDENT TRANSCRIPTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

Acta Poloniae Pharmaceutica - Drug Research ◽

10.32383/appdr/114081 ◽

2020 ◽

Vol 77 (1) ◽

pp. 77-88 ◽

Cited By ~ 1

Author(s):

Jarosław Paluszczak ◽

Robert Kleszcz ◽

Olga Witczak ◽

Violetta Krajka-Kuźniak

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Neck Squamous Cell Carcinoma ◽

Squamous Cell Carcinoma Cell ◽

Carcinoma Cell Lines

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Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma

International Journal of Oral Science ◽

10.1038/s41368-021-00131-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Areeg Elmusrati ◽

Justin Wang ◽

Cun-Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Immune System ◽

Tumor Microenvironment ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

High Morbidity ◽

Advanced Therapies

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

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Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13123038 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3038

Author(s):

Mickaël Burgy ◽

Aude Jehl ◽

Ombline Conrad ◽

Sophie Foppolo ◽

Véronique Bruban ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Cell Cycle Progression ◽

Locally Advanced ◽

Treatment Resistance ◽

Neck Squamous Cell Carcinoma ◽

Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

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Differences in Extracellular Vesicle Protein Cargo Are Dependent on Head and Neck Squamous Cell Carcinoma Cell of Origin and Human Papillomavirus Status

Cancers ◽

10.3390/cancers13153714 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3714

Author(s):

Christine Goudsmit ◽

Felipe da Veiga Leprevost ◽

Venkatesha Basrur ◽

Lila Peters ◽

Alexey Nesvizhskii ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Extracellular Vesicle ◽

Neck Squamous Cell Carcinoma ◽

Cytokeratin 19 ◽

Oral Keratinocytes ◽

Transformed Cell Lines

To identify potential extracellular vesicle (EV) biomarkers in head and neck squamous cell carcinoma (HNSCC), we evaluated EV protein cargo and whole cell lysates (WCL) from HPV-positive and -negative HNSCC cell lines, as well as normal oral keratinocytes and HPV16-transformed cells. EVs were isolated from serum-depleted, conditioned cell culture media by polyethylene glycol (PEG) precipitation/ultracentrifugation. EV and WCL preparations were analyzed by LC-MS/MS. Candidate proteins detected at significantly higher levels in EV compared with WCL, or compared with EV from normal oral keratinocytes, were identified and confirmed by Wes Simple Western protein analysis. Our findings suggest that these proteins may be potential HNSCC EV markers as proteins that may be (1) selectively included in EV cargo for export from the cell as a strategy for metastasis, tumor cell survival, or modification of tumor microenvironment, or (2) representative of originating cell composition, which may be developed for diagnostic or prognostic use in clinical liquid biopsy applications. This work demonstrates that our method can be used to reliably detect EV proteins from HNSCC, normal keratinocyte, and transformed cell lines. Furthermore, this work has identified HNSCC EV protein candidates for continued evaluation, specifically tenascin-C, HLA-A, E-cadherin, EGFR, EPHA2, and cytokeratin 19.

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Kaempferol Induces Cell Death and Sensitizes Human Head and Neck Squamous Cell Carcinoma Cell Lines to Cisplatin

10.1007/5584_2020_603 ◽

2020 ◽

Author(s):

Mabel Catalán ◽

Catalina Rodríguez ◽

Ivonne Olmedo ◽

Javiera Carrasco-Rojas ◽

Diego Rojas ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Death ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Human Head ◽

Neck Squamous Cell Carcinoma ◽

Carcinoma Cell Lines

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YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

Cells ◽

10.3390/cells9051281 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1281 ◽

Cited By ~ 3

Author(s):

Kacper Guglas ◽

Tomasz Kolenda ◽

Maciej Stasiak ◽

Magda Kopczyńska ◽

Anna Teresiak ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

High Expression ◽

Ribonucleoprotein Particle ◽

Hnscc Cell

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

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