Browsing by Autor "Romina Andrea Quiroga"

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    Analysis of the protumoral mechanisms of <i>F.nucleatum</i> on growth, epithelial-mesenchymal transition and the expression of immunosuppressive markers in cell line of OSCC
    (American Association of Immunologists, 2023) Camila Paz Munoz; Luciano Ferrada; Erick Riquelme; Felipe Zúñiga; Wilfredo González; Daniel Betancur; Ángel Oñate; Sergio Andrés Sanhueza Novoa; Camilo Daniel Cabrera-Garcia; Romina Andrea Quiroga
    Abstract Background Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, and preliminary data from our laboratory has identified Fusobacterium nucleatum (F.n) and Epithelial Mesenchymal Transition (EMT) markers in the secretome of biopsies from patients with OSCC in comparison with healthy biopsies from the oral cavity. However, the mechanisms modulated by the tumoral bacteriome in OSCC remains not fully understood. Methods Oral cancer cells (HSC3) were infected with F.n using a MOI of 100 to evaluate the effect of the bacteria on tumor growth, expression of EMT markers and immunomodulatory properties. Results After infection, we confirmed the presence of bacteria inside and surrounding the cancer cells by confocal microscopy. Then, a significant increment in the size of F.n-infected tumor spheroids was found at 3-, 6- and 10-days post-infection. Related to EMT markers, MMP-9 transcripts were significantly elevated in infected cells, whereas E-cadherin transcripts were significantly downregulated post infection. In addition, the Human XL Oncology array kit revealed that several cancer proteins such as MMP-3, GM-CSF, FOXO1/FKHR, Cathepsina D-S, Amphiregulin, SerpinB5/Maspin and EGFR were upregulated and others like ICAM-1, DLL-1 and ERB2 were downregulated after F.n-infection. Finally, the expression of Galectin-9 measured by flow cytometry was significantly increased in infected cells than control cancer cells. Conclusions The periodontal bacterium F.n promotes tumor progression of OSCC through increased tumor growth, acquisition of ETM-associated markers and Galectin-9 upregulation. Fondecyt Regular Project 1211480
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    EFFECT OF ARTIFICIAL MITOCHONDRIAL TRANSFER FROM LINE CELLULAR HSC-3 TO LYMPHOCYTE TCD4+, AS A MECHANISM INDUCTOR OF EXHAUSTED PHENOTYPE
    (American Association of Immunologists, 2023) Bárbara Evelyn Antilef Cáceres; Solange Estefania Cisterna; Romina Andrea Quiroga; Sergio Andrés Sanhueza Novoa; Camilo Daniel Cabrera-Garcia; Camila Paz Muñoz Grez; Felipe Zúñiga; Luciano Ferrada; Wilfredo L. Gonzáles; P. A. C. Luz
    Abstract Background Oral squamous cell carcinoma (OSCC) is the most frequent type of oral cancer. The tumor microenvironment of OSCC induces an alteration of the T lymphocyte, promoting an exhausted phenotype. The main organelle of metabolism is the mitochondrion and in recent years it has been indicated that several cells have the capacity to transfer mitochondria, including cancer cells. However, it has not been evaluated whether mitochondria transfer from cancer cells to T lymphocytes induces an exhausted phenotype in T lymphocyte. The aim of this work was to analyze the exhausted phenotype in TCD4+ lymphocytes after artificial transfer of mitochondria (MitoCeption) obtained from the oral cancer cell line HSC-3. Methods Isolated MitoTracker-labeled mitochondria from oral cancer tumor cells were Mitocepted into CD4+ T lymphocytes. Then, surface molecule expression, proliferation and cytokine secretion mediated by tumor mitochondrial transfer were analyzed by flow cytometry. Results The results showed that TCD4+ lymphocytes that acquired mitochondria had increased expression of 2 inhibitory proteins (TIGIT and CTLA4) and 3 proteins associated with exhausted phenotype (PD-1, PLD-1 and LAG3), compared to the control group. In addition, the mitocepted lymphocytes exhibited a significant decrease in proliferation compared to the control. For cytokine analysis, a significant decrease was observed in the mitocepted group in the secretion of IFN-gamma, TNF-alpha, IL-10 and IL-4, but not IL-17, compared to the control. Conclusions Therefore, we concluded that the acquisition of isolated mitochondria from HSC-3 cancer cells by CD4+ T lymphocyte induces an exhausted phenotype in the TCD4+ lymphocyte. Regular Fondecyt Project 1211480