Establishment of syngeneic murine model for oral cancer therapy

Chen, Yi‐Fen; Chang, Kuo‐Wei; Yang, I-Ting; Tu, Hsi-Feng; Lin, Shih-Yao

doi:10.1016/j.oraloncology.2019.06.026

Cited by 22 publications

(29 citation statements)

References 31 publications

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“…Moreover, the use of ex vivo bioluminescence imaging in our study allowed us to detect lung and lymph node metastases that were not visible by in vivo imaging. The usefulness of this imaging technique to detect metastatic cells was also reported in other mouse models of OSCC (Bais et al., 2015; Braks et al., 2015; Chen, Chang, et al, 2019; Chen, Liu, et al, 2019; Masood et al., 2013). However, the bioluminescence imaging presents some limitations such as a transient and variable signal when compared to fluorescence imaging (Bais et al., 2015).…”

Section: Discussionsupporting

confidence: 60%

“…Indeed, this procedure has previously been reported only for lymph node metastasis (Masood et al., 2013; Matsui et al., 1998). This allowed us to obtain large and diffuse lung metastases in 60% of the injected animals by week 3 by injecting a lower number of cells (0.5 × 10 6 ) than previous studies (Chen, Chang, et al, 2019; Hyakusoku et al., 2016; Li et al., 2012), indicating the high metastatic potential of HSC‐3 M1 cell line. In addition, the prevalence and the distribution of lung metastases in both lungs were consistent with previous studies (Hyakusoku et al., 2016; Li et al., 2012, 2018).…”

Section: Discussionmentioning

confidence: 91%

“…However, the authors did not provide any information about the possible presence of lung metastasis. In contrast, other studies correlated the high level of aggressiveness and distant metastatic potential of OSCC cell lines with the expression of other CSCs markers such as OCT‐4, ALDH1, and SOX2 and proliferation markers (Chen, Chang, et al, 2019; Chen, Liu, et al, 2019; Masood et al., 2013). Nevertheless, more investigations are needed in order to elucidate the role of EMT and CSCs in OSCC metastatic dissemination.…”

Section: Discussionmentioning

confidence: 93%

“…More recently, a syngeneic model reported by Chen, Liu, et al (2019) developed both lymph node and lung metastases 8 weeks after the orthotopic implantation of cells derived from 4NQO‐induced OSCC (5 × 10 6 cells, MOC‐L1‐Luc murine cell subclone). However, the majority of developed orthotopic models of OSCC had no or very few lung metastases, probably due to the fast growth of the primary tumor and/or a high number of injected OSCC cells (e.g., 0.2–5 × 10 6 ) accompanied by an early sacrifice of the animals (3–3.5 weeks) (Chen, Chang, Yang, Tu, & Lin, 2019; Matsui et al., 1998; Noguchi et al., 2003; Umeda et al., 2001).…”

Section: Discussionmentioning

confidence: 99%

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Development of lung metastases in mouse models of tongue squamous cell carcinoma

et al. 2020

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Objective Oral squamous cell carcinoma (OSCC) represents 3%–4% of all cancers. Despite the increasing incidence of OSCC distant metastasis and poor prognosis, few animal models of OSCC distant metastasis have been reported. In this study, we established mouse models of OSCC lung metastasis by orthotopic and tail vein injection of new OSCC cell lines. Methods For the tail vein model, we used a novel cell line isolated from lung metastases reproduced in vivo after intravenous injection of HSC‐3 GFP/luciferase cells and sorted for GFP expression (HSC‐3 M1 GFP/luciferase). Lung metastases were assessed by imaging techniques and further confirmed by histology. For the orthotopic model, HSC‐3 GFP/luciferase cells were injected into the tongue of athymic nude mice. The primary tumor and metastases were assessed by in vivo imaging, histology, and immunohistochemistry. Results The orthotopic model presented spontaneous lung metastases in 50% of the animals and lymph node metastases were present in 83% of cases. In the tail vein model, a lung metastasis rate of 60% was observed. Conclusions Lung metastases were successfully reproduced by orthotopic and tail vein injection. Since lymph node metastases were present, the orthotopic model with HSC‐3 GFP/luciferase cells may be suitable to investigate metastatic dissemination in OSCC.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Development of lung metastases in mouse models of tongue squamous cell carcinoma

et al. 2020

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“…Nagaya et al have previously developed murine OSCC models with varying immunogenicity to demonstrate the therapeutic potential of photoimmunotherapy targeting the stem cell marker CD44 [20]. Recently, Chen et al have recently developed and examined the response of murine OSCC lines to chemotherapy and immune therapy [21,22]. Despite the well-documented two-way interaction between the immune system and radiation therapy [23][24][25], only a few studies have examined the effects of radiation against OSCC in immunocompetent hosts [26,27].…”

Section: Introductionmentioning

confidence: 99%

Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts

Vincent‐Chong

Seshadri

2020

Cancers

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Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD50 for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease.

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Targeting tumor O‐glycosylation modulates cancer–immune‐cell crosstalk and enhances anti‐PD‐1 immunotherapy in head and neck cancer

Lin

Chuang

et al. 2023

Molecular Oncology

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Cells in the tumor microenvironment (TME) communicate via membrane‐bound and secreted proteins, which are mostly glycosylated. Altered glycomes of malignant tumors influence behaviors of stromal cells. In this study, we showed that the loss of core‐1 β1,3‐galactosyltransferase (C1GALT1)‐mediated O‐glycosylation suppressed tumor growth in syngeneic head and neck cancer mouse models. O‐glycan truncation in tumor cells promoted the M1 polarization of macrophages, enhanced T‐cell‐mediated cytotoxicity, and reduced interleukin‐6 (IL‐6) levels in the secretome. Proteasomal degradation of IL‐6 was controlled by the O‐glycan at threonine 166. Both IL‐6/IL‐6R blockade and O‐glycan truncation in tumor cells induced similar pro‐inflammatory phenotypes in macrophages and cytotoxic T lymphocytes (CTLs). The combination of the O‐glycosylation inhibitor itraconazole and anti‐programmed cell death protein 1 (anti‐PD‐1) antibody effectively suppressed tumor growth in vivo. Collectively, our findings demonstrate that O‐glycosylation in tumor cells governs their crosstalk with macrophages and CTLs. Thus, targeting O‐glycosylation successfully reshapes the TME and consequently enhances the efficacy of anti‐PD‐1 therapy.

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Establishment of syngeneic murine model for oral cancer therapy

Cited by 22 publications

References 31 publications

Development of lung metastases in mouse models of tongue squamous cell carcinoma

Development of lung metastases in mouse models of tongue squamous cell carcinoma

Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts

Targeting tumor O‐glycosylation modulates cancer–immune‐cell crosstalk and enhances anti‐PD‐1 immunotherapy in head and neck cancer

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