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Mouse models of oral cancer. Abbreviations: NOD, nonobese diabetic; SCID, severe combined immunodeficiency; NSG, NOD/SCID gamma.
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Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to can...
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Citations
... The emergence of tumor-like lesions in immunosuppressed SCID mice after p53 core fibrils injection supports the link between p53 amyloid and cancer initiation. Further, the role of the immune system was assessed by using immunocompetent (C57BL/6) mice which showed delayed tumor induction and a lower rate of tumorigenesis [37]. However, any direct mechanism of immune modulation by p53 amyloids is still unexplored. ...
... NOG mice offer several advantages over other immunocompromised mice, including high xenograft efficiency with injecting only a few cancer cells or tissues and the complete absence of rejection. These mice can survive for more than 1 and a half years under pathogen-free conditions due to the lack of T and B cell leakiness typically observed in NSG mice [91]. This makes NOG mice an attractive choice for CRC xenograft studies, as they provide a more stable and supportive environment for studying human cancer in vivo. ...
... Examples of immunodeficient strains used and their immunological characteristics are shown in Table 2. There are also animals whose murine hematopoietic system has been replaced by human hematopoietic stem cells in the bone marrow to reconstitute the human immune system, avoiding the rejection of human-derived tumor by animals [65,66]. ...
Introduction:
Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose.
Area covered:
This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer.
Expert opinion:
Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.
... This is where a human tumour xenograft on nude mice, SCID mice, or NOD/ SCID humanised mice can be helpful. Particularly when in vitro findings are needed to be confirmed in vivo, these models have been utilised extensively to examine the molecular mechanism of the antitumor impact of therapeutic drugs, combination therapies, metastasis and invasion, epithelial-mesenchymal transition, and cancer stem cells (CSCs) [82]. Immunocompromised or immunodeficient mice lack specific genes leading to reduced or no expression in certain cells. ...
Murine models are widely used in scientific research because they share many genetic similarities with humans, making them a valuable tool for studying various diseases. C57BL/6 is an experimental mouse model to study the demyelination and inflammation etiology of Multiple Sclerosis (MS). Intracranial inoculation of neurotropic murine β-coronavirus strain of Mouse hepatitis virus in C57BL/6 mice induces demyelination with or without axonal loss, providing many insights regarding the mechanism of MS as well as SARS-CoV-2 mediated pulmonary and neuro pathology in humans. By selectively using knockout mice in the wild-type C57BL/6 background, researchers can gain insights into the immunomodulatory nexus and can identify pathways involved in immune regulation which further can be efficiently studied with CD4-/-, CD40-/- and CD40L-/- mice. In addition, C57BL/6 mice can also be used to generate syngeneic mouse models to investigate the etiology and mechanism of various cancers, including ovarian cancer. Similarly, along with C57BL/6 mice, different immunocompromised mice models, such as nude mice, SCID mice, and NOD/SCID mice, can be used to study the etiology, host-tumour interaction, function of the microenvironment, and tumour heterogeneity in tumour metastasis.
... Since HPV can only infect human cells, there is a lack of immunocompetent mouse models of HPV-positive OSCC. The majority of the in vivo models used in preclinical research are xenograft mouse models using cells originating from patient-derived HPV-positive tumors transplanted into immunodeficient athymic nude mice, which are not suitable for immunologic studies [33][34][35][36][37]. ...
Background
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 HPV-positive 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 HPV-16 oncogenes E6 and E7 in the MOC1 OSCC cell line using retroviral transduction. After confirming stable expression of HPV-16 E6 and E7 with quantitative real-time PCR and immunofluorescence 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, immunofluorescence 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 confirmed stable expression of HPV-16 oncogenes and differences in cell morphology, in vitro migration capacity, and tumor microenvironment characteristics. Although the cell lines did not differ in their intrinsic radiosensitivity, one of the HPV-positive tumor models, MOC1-HPV K1, showed a significantly 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 profile of MOC1-HPV cell lines.
Conclusions
In conclusion, we developed and characterized a novel immunocompetent mouse model of HPV-positive OSCC that exhibits increased radiosensitivity and enables studies of immune-based treatment approaches in HPV-positive OSCC.
... The 4-NQO model of rat palate carcinoma and human clinical disease has similar histological progressions (Nauta et al., 1996). Induced tumours tend to be less clinically aggressive and more highly differentiated than those observed in humans (Lei et al., 2016). Some rat models in oral cancer research are listed in Table 1. ...
Cancer is a leading cause of death worldwide, but advances in treatment, early detection, and prevention have helped to reduce its impact. To translate cancer research findings into clinical interventions for patients, appropriate animal experimental models, particularly in oral cancer therapy, can be helpful. In vitro experiments using animal or human cells can provide insight into cancer's biochemical pathways. This review discusses the various animal models used in recent years for research and clinical intervention in oral cancer, along with their advantages and disadvantages. We highlight the advantages and limitations of the used animal models in oral cancer research and therapy by searching the terms of animal models, oral cancer, oral cancer therapy, oral cancer research, and animals to find all relevant publications during 2010‐2023. Mouse models, widely used in cancer research, can help us understand protein and gene functions in vivo and molecular pathways more deeply. To induce cancer in rodents, xenografts are often used, but companion animals with spontaneous tumours are underutilized for rapid advancement in human and veterinary cancer treatments. Like humans with cancer, companion animals exhibit biological behaviour, treatment responses, and cytotoxic agent responses similar to humans. In companion animal models, disease progression is more rapid, and the animals have a shorter lifespan. Animal models allow researchers to study how immune cells interact with cancer cells and how they can be targeted specifically. Additionally, animal models have been extensively used in research on oral cancers, so researchers can use existing knowledge and tools to better understand oral cancers using animal models.
... Although a signi cant proportion of OSCCs are associated with HPV infection, there is a lack of preclinical immunocompetent mouse models due to the species speci city of HPV. The majority of the models used in preclinical research are xenograft mouse models using cells originating from patientderived HPV-positive tumors transplanted into immunode cient athymic nude mice, which are not suitable for immunologic studies [27][28][29][30][31]. ...
Background
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, due to the species specificity of HPV, 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 HPV-positive 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 HPV-16 oncogenes E6 and E7 in the MOC1 OSCC cell line using retroviral transduction. After confirming stable expression of HPV-16 E6 and E7 with quantitative real-time PCR and immunofluorescence 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, immunofluorescence 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 confirmed stable expression of HPV-16 oncogenes and differences in cell morphology, in vitro migration capacity, and tumor microenvironment characteristics. Although the cell lines did not differ in their intrinsic radiosensitivity, one of the HPV-positive tumor models, MOC1-HPV K1, showed a significantly 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 profile of MOC1-HPV cell lines.
Conclusions
In conclusion, we developed and characterized a novel immunocompetent mouse model of HPV-positive OSCC that exhibits increased radiosensitivity and enables studies of immune-based treatment approaches in HPV-positive OSCC.
... [14][15][16][17][18] However, each of these models has its own disadvantages, like the Matrigel invasion assay is extensively attributed to variability and the nude mice model needs to be artificially immunocompromised and fails to lay out a natural environment for tumor development. [19,20] The chorioallantoic membrane (CAM) assay offers to be an admissible alternative to the above-mentioned models and can be employed to study tumor invasion in real time and it, together with extracellular matrix protein (ECM), imitates the true microenvironment of the basement membrane, allowing for tumor development. [21] Chick CAM is an extraembryonic structure identical to the placenta in mammals. ...
Purpose:
To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient-derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity.
Methods:
Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient-derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor-embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion.
Results:
Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross-sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki-67 positivity in Immunohistochemistry (IHC).
Conclusion:
The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient-specific tumors for preclinical drug screening.
... To address that, many in vivo models are available in the field, each with their own advantages and disadvantages. Immune competent models considered usually include chemically induced models, syngeneic transplanted models, and genetically engineered models [32]. A key barrier to the engraftment of human cancer cells in immunocompetent rodents is robust xenogeneic immune rejection [33]. ...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Current therapies often provide marginal survival benefits at the expense of undesirable side effects. Oncolytic viruses represent a novel strategy for the treatment of HCC due to their inherent ability to cause direct tumor cell lysis while sparing normal tissue and their capacity to stimulate potent immune responses directed against uninfected tumor cells and distant metastases. Oncolytic virotherapy (OVT) is a promising cancer treatment, but before it can become a standard option in practice, several challenges-systemic viral delivery optimization/enhancement, inter-tumoral virus dispersion, anti-cancer immunity cross-priming, and lack of artificial model systems-need to be addressed. Addressing these will require an in vivo model that accurately mimics the tumor microenvironment and allows the scientific community to design a more precise and accurate OVT. Due to their close physiologic resemblance to humans, murine cancer models are the likely preferred candidates. To provide an accurate assessment of the current state of in vivo OVT in HCC, we have reviewed a comprehensively searched body of work using murine in vivo HCC models for OVT.
... Most cancer vaccination studies rely on xenograft transplantation into immunodeficient mice models (Hidalgo et al. 2014;Lei et al. 2016). These models due to the lack of a competent immune system may not exactly represent disease progression and the therapeutic outcomes. ...
Background
Cancer stem cells (CSCs), a rare sub-fraction of tumor cells, with the capability of self-renewal and strong oncogenicity are tightly responsible for chemo and radio resistance and tumor metastasis in colorectal cancer. Hence, CSCs targeting would improve the efficacy of therapeutic strategies and clinical outcomes.Methods
Here, using three-dimensional CSC spheroids and syngeneic mice model, we evaluated the cancer preventive impact of CSCs-based vaccination. CSCs enrichment was performed via colonosphere formation from CT-26 cell line and CT-26-derived tumor biopsy and characterized by confirming high expression of key stemness genes (OCT4, SOX2, and NANOG) and CSC-related surface biomarkers (CD166, DCLK1, and CD133) via real-time PCR and flow cytometry, respectively. Then, the stemness phenotype and self-renewal in CSC-enriched spheroids were further confirmed by showing serial sphere formation capacity, clonogenicity potential, and enhanced in vivo tumorigenic capacity compared to their parental counterparts. CSCs lysates were used as vaccines in prophylactic settings compared to the parental cell lysate and PBS groups.ResultImmunization of syngeneic mice with CSCs lysates was effective in the prevention of tumor establishment and significantly decreased tumor growth rate accompanied by an improvement in survival rate in tumor-bearing mice compared to groups subjected to parental cells lysate and PBS. These results, for the first time, showed that mice immunized with cell lysate from tumor biopsy-derived spheroids are resistant to tumor induction. Immunofluorescence staining indicated that only the serum antibodies from CSC-vaccinated mice reacted with colonospheres.Conclusions
These findings represent CSCs lysate-based vaccination as a potential approach to hampering immunotherapy failure of colorectal cancer which along with other traditional therapies may effectively apply to prevent the establishment of aggressive tumors harboring stemness features.
