Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Sara Peixoto da Silva (Author) Other; Joana M. O. Santos (Author) Other; Verónica F. Mestre (Author) Other; Beatriz Medeiros Fonseca (Author) Other; Paula A. Oliveira (Author) Other; Margarida M. S. M. Bastos (Author) FEUP; Rui M. Gil da Costa (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: International Journal Of Molecular Sciences

Vol. 21 No. 7

Pages: 1-17

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00S-FXJ

DOI: 10.3390/ijms21145020

Abstract (EN): Cancer cachexia is a multifactorial syndrome characterized by general inflammation, weight loss and muscle wasting, partly mediated by ubiquitin ligases such as atrogin-1, encoded byFbxo32. Cancers induced by high-risk human papillomavirus (HPV) include anogenital cancers and some head-and-neck cancers and are often associated with cachexia. The aim of this study was to assess the presence of cancer cachexia in HPV16-transgenic mice with or without exposure to the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Male mice expressing the HPV16 early region under the control of the cytokeratin 14 gene promoter (K14-HPV16; HPV+) and matched wild-type mice (HPV-) received DMBA (or vehicle) topically over 17 weeks of the experiment. Food intake and body weight were assessed weekly. The gastrocnemius weights andFbxo32expression levels were quantified at sacrifice time. HPV-16-associated lesions in different anatomic regions were classified histologically. Although unexposed HPV(+)mice showed higher food intake than wild-type matched group (p < 0.01), they presented lower body weights (p < 0.05). This body weight trend was more pronounced when comparing DMBA-exposed groups (p < 0.01). The same pattern was observed in the gastrocnemius weights (between the unexposed groups:p < 0.05; between the exposed groups:p < 0.001). Importantly, DMBA reduced body and gastrocnemius weights (p < 0.01) when comparing the HPV(+)groups. Moreover, theFbxo32gene was overexpressed in DMBA-exposed HPV(+)compared to control mice (p< 0.05). These results show that K14-HPV16 mice closely reproduce the anatomic and molecular changes associated with cancer cachexia and may be a good model for preclinical studies concerning the pathogenesis of this syndrome.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17