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

Data de publicação:

Autores da FMUP

  • Rui Manuel De Medeiros Melo Silva

    Autor

Participantes de fora da FMUP

  • da Silva, SP
  • Santos, JMO
  • Mestre, VF
  • Medeiros-Fonseca, B
  • Oliveira, PA
  • Bastos, MMSM
  • da Costa, RMG

Abstract

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.

Dados da publicação

ISSN/ISSNe:
1661-6596, 1661-6596

International Journal of Molecular Sciences  Multidisciplinary Digital Publishing Institute (MDPI)

Tipo:
Article
Páginas:
-

Citações Recebidas na Web of Science: 4

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Keywords

  • cancer cachexia; HPV16; K14-HPV16; mouse model; DMBA; wasting syndrome

Financiamento

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