VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • HPV-positive murine oral squamous cell carcinoma : development and characterization of a new mouse tumor model for immunological studies [Elektronski vir]
    Modic, Živa ...
    Infection with high-risk human papillomavirus (HPV) strains is one of the risk factors for the development of oral squamous cell carcinoma (OSCC). Some patients with HPV-positive OSCC have a better ... prognosis and respond better to various treatment modalities, including radiotherapy or immunotherapy. However, since HPV can only infect human cells, there are only a few immunocompetent mouse models available that enable immunological studies. Therefore, the aim of our study was to develop a transplantable immunocompetent mouse model of HPVpositive OSCC and characterize it in vitro and in vivo. Methods Two monoclonal HPV-positive OSCC mouse cell lines were established by inducing the expression of HPV16 oncogenes E6 and E7 in the MOC1 OSCC cell line using retroviral transduction. After confrming stable expression of HPV-16 E6 and E7 with quantitative real-time PCR and immunofuorescence staining, the cell lines were further characterized in vitro using proliferation assay, wound healing assay, clonogenic assay and RNA sequencing. In addition, tumor models were characterized in vivo in C57Bl/6NCrl mice in terms of their histological properties, tumor growth kinetics, and radiosensitivity. Furthermore, immunofuorescence staining of blood vessels, hypoxic areas, proliferating cells and immune cells was performed to characterize the tumor microenvironment of all three tumor models. Results Characterization of the resulting MOC1-HPV cell lines and tumor models confrmed stable expression of HPV16 oncogenes and diferences in cell morphology, in vitro migration capacity, and tumor microenvironment characteristics. Although the cell lines did not difer in their intrinsic radiosensitivity, one of the HPV-positive tumor models, MOC1-HPV K1, showed a signifcantly longer growth delay after irradiation with a single dose of 15 Gy compared to parental MOC1 tumors. Consistent with this, MOC1-HPV K1 tumors had a lower percentage of hypoxic tumor area and a higher percentage of proliferating cells. Characteristics of the newly developed HPV-positive OSCC tumor models correlate with the transcriptomic profle of MOC1-HPV cell lines.
    Vir: Journal of translational medicine. - ISSN 1479-5876 (Vol. 21, no. 376, 2023, str. [1-20])
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2023
    Jezik - angleški
    COBISS.SI-ID - 154591491

    Povezava(-e):

    https://doi.org/10.1186/s12967-023-04221-4
    Repozitorij Univerze v Ljubljani – RUL
    DOI

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