Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer.

Details

Serval ID
serval:BIB_F05A2D65979F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer.
Journal
International journal of cancer
Author(s)
Mermod M., Hiou-Feige A., Bovay E., Roh V., Sponarova J., Bongiovanni M., Vermeer D.W., Lee J.H., Petrova T.V., Rivals J.P., Monnier Y., Tolstonog G.V., Simon C.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Publication state
Published
Issued date
15/06/2018
Peer-reviewed
Oui
Volume
142
Number
12
Pages
2518-2528
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
HPV-positive head and neck squamous cell carcinoma (HNSCC) is increasingly frequent. Management is particularly debated in the case of postsurgical high-risk features, that is, positive surgical margins and extracapsular spread (ECS). In this increasingly complex emerging framework of HNSCC treatment, representative preclinical models are needed to support future clinical trials and advances in personalized medicine. Here, we present an immunocompetent mouse model based on the implantation of mouse tonsil epithelial HPV16-E6/E7-expressing cancer cells into the submental region of the floor-of-the-mouth. Primary tumors were found to replicate the patterns of human HNSCC local invasion and lymphatic dissemination. To study disease progression after surgery, tumors were removed likely leaving behind residual disease. Surgical resection of tumors was followed by a high rate of local recurrences (>90%) within the first 2-3 weeks. While only 50% of mice had lymph node metastases (LNM) at time of primary tumor excision, all mice with recurrent tumors showed evidence of LNM. To study the consecutive steps of LNM progression and distant metastasis development, LNs from tumor-bearing mice were transplanted into naïve recipient mice. Using this approach, transplanted LNs were found to recapitulate all stages and relevant histological features of regional metastasis progression, including ECS and metastatic spread to the lungs. Altogether, we have developed an immunocompetent HPV-positive HNSCC mouse model of postsurgical local recurrence and regional and distant metastasis progression suitable for preclinical studies.
Keywords
HNSCC, HPV, metastasis, minimal residual disease, mouse model, recurrence, surgery
Pubmed
Web of science
Create date
10/01/2018 14:20
Last modification date
20/08/2019 16:18
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