An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

Carper, Miranda B.; Troutman, Scott; Wagner, Bethany L.; Byrd, Kevin M.; Selitsky, Sara R.; Parag-Sharma, Kshitij; Henry, Erin C.; Liu, Weimin; Parker, Joel S.; Montgomery, Stephanie A.; Cleveland, John L.; Williams, Scott; Kissil, Joseph L.; Hayes, D. Neil; Amelio, Antonio L.

doi:10.1016/j.celrep.2019.10.005

Cited by 24 publications

(22 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, HPV-positive mice developed oral tumors rather than oropharyngeal cancers commonly seen in HNSCC patients. Caper et al (198) established a novel inducible GEMM of HPV-related OPSCC, in which the HPV16 oncogenes were activated in a tissue-specific and temporal The Kras G12D oncogene driven by the K5 or K14 promoter was distributed under the control of Cre recombinase fused to a mutant of the human progesterone receptor Administration of RU486 for 16-24 weeks induced the overexpression of oncogenic K-ras G12D in the oral epithelium of mice and resulted in the development of squamous papillomas in the oral cavity.…”

Section: Gemms Of Hpv-related Oral Cancermentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.

show abstract

Section: Gemms Of Hpv-related Oral Cancermentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Many other studies were conducted with the aim to investigate antitumor effects in HPV+ murine models, so Li et al recently published that their candidate vaccine against HPV16E7 significantly reduced Treg and MDSCs infiltration in mouse genital tumors [104,105]. Given the creation of a new immunocompetent mouse model of HPV16+ head and neck squamous cell carcinoma [106], this promising vaccination strategy should be considered and tested for the treatment of HPV+ oropharyngeal SCC.…”

Section: Myeloid Cellsmentioning

confidence: 99%

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

Lechien

Descamps

Seminerio

et al. 2020

Cancers

View full text Add to dashboard Cite

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses.

show abstract

“…Collagen fibers were observed under polarized light microscopy. Immunohistochemistry was performed as previously described [6] .…”

Section: Methodsmentioning

confidence: 99%

Lysyl hydroxylase 2-induced collagen cross-link switching promotes metastasis in head and neck squamous cell carcinomas

et al. 2021

Self Cite

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. HNSCC patient prognosis is closely related to the occurrence of tumor metastases, and collagen within the tumor microenvironment (TME) plays a key role in this process. Lysyl hydroxylase 2 (LH2), encoded by the Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2 ( PLOD2 ) gene, catalyzes hydroxylation of telopeptidyl lysine (Lys) residues of fibrillar collagens which then undergo subsequent modifications to form stable intermolecular cross-links that change the biomechanical properties (i.e. quality) of the TME. While LH2-catalyzed collagen modification has been implicated in driving tumor progression and metastasis in diverse cancers, little is known about its role in HNSCC progression. Thus, using gain- and loss-of-function studies, we examined the effects of LH2 expression levels on collagen cross-linking and cell behavior in vitro and in vivo using a tractable bioluminescent imaging-based orthotopic xenograft model. We found that LH2 overexpression dramatically increases HNSCC cell migratory and invasive abilities in vitro and that LH2-driven changes in collagen cross-linking robustly induces metastasis in vivo . Specifically, the amount of LH2-mediated collagen cross-links increased significantly with PLOD2 overexpression, without affecting the total quantity of collagen cross-links. Conversely, LH2 knockdown significantly blunted HNSCC cells invasive capacity in vitro and metastatic potential in vivo . Thus, regardless of the total “quantity” of collagen crosslinks, it is the “quality” of these cross-links that is the key driver of HNSCC tumor metastatic dissemination. These data implicate LH2 as a key regulator of HNSCC tumor invasion and metastasis by modulating collagen cross-link quality and suggest that therapeutic strategies targeting LH2-mediated collagen cross-linking in the TME may be effective in controlling tumor progression and improving disease outcomes.

show abstract

An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

Cited by 24 publications

References 80 publications

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas

Lysyl hydroxylase 2-induced collagen cross-link switching promotes metastasis in head and neck squamous cell carcinomas

Contact Info

Product

Resources

About