Establishment of basal cell carcinoma animal model in Chinese tree shrew ( Tupaia belangeri chinensis)

Zool Res. 2017 Jul 18;38(4):180-190. doi: 10.24272/j.issn.2095-8137.2017.045.

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog (Hh) signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened (Smo) used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lentiviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future drug discoveries.

Keywords: Basal cell carcinoma; Chinese tree shrew; Hedgehog.

MeSH terms

  • Animals
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / pathology*
  • Disease Models, Animal*
  • Gene Expression Regulation, Neoplastic
  • Genetic Engineering
  • Humans
  • Male
  • Mutation
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*
  • Smoothened Receptor / genetics
  • Smoothened Receptor / metabolism
  • Tail
  • Tupaia*

Substances

  • Smoothened Receptor

Grant support

This study was supported by the National Key Research and Development Program of China (2016YFA0100900),the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13000000),the National Nature Science Foundation of China (U1502224,81672764),and the Yunnan Applied Basic Research Projects (2014FA038,2016FA009,2014FB182).C.P.Y was also supported by the Chinese Academy of Sciences Western Light Program,Youth Innovation Promotion Association,CAS.