Volume 38 Issue 4
Jul.  2017
Turn off MathJax
Article Contents
Li-Ping Jiang, Qiu-Shuo Shen, Cui-Ping Yang, Yong-Bin Chen. Establishment of basal cell carcinoma animal model in Chinese tree shrew (Tupaia belangeri chinensis). Zoological Research, 2017, 38(4): 180-190. doi: 10.24272/j.issn.2095-8137.2017.045
Citation: Li-Ping Jiang, Qiu-Shuo Shen, Cui-Ping Yang, Yong-Bin Chen. Establishment of basal cell carcinoma animal model in Chinese tree shrew (Tupaia belangeri chinensis). Zoological Research, 2017, 38(4): 180-190. doi: 10.24272/j.issn.2095-8137.2017.045

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

doi: 10.24272/j.issn.2095-8137.2017.045
Funds:  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.
More Information
  • Corresponding author: Yong-Bin Chen, ybchen@mail.kiz.ac.cn; Cui-Ping Yang, cuipingyang@mail.kiz.ac.cn
  • Received Date: 2017-03-05
  • Rev Recd Date: 2017-06-25
  • Publish Date: 2017-07-18
  • 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.
  • loading
  • [1]
    Abarca JF, Casiccia CC. 2002. Skin cancer and ultraviolet-B radiation under the Antarctic ozone hole: southern Chile, 1987-2000. Photodermatology, Photoimmunology & Photomedicine, 18(6): 294-302.
    Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M. 2010.Pathogenesis of hepatitis C virus infection in Tupaia belangeri. Journal of Virology, 84(1): 303-311.
    Arad S, Zattra E, Hebert J, Epstein EH, Jr., Goukassian DA, Gilchrest BA. 2008. Topical thymidine dinucleotide treatment reduces development of ultraviolet-induced basal cell carcinoma in Ptch-1+/- mice. The American Journal of Pathology, 172(5): 1248-1255.
    Asgari MM, Moffet HH, Ray GT, Quesenberry CP. 2015. Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998-2012. JAMA Dermatology, 151(9): 976-981.
    Aszterbaum M, Beech J, Epstein EH, Jr. 1999. Ultraviolet radiation mutagenesis of hedgehog pathway genes in basal cell carcinomas. Journal of Investigative Dermatology Symposium Proceedings, 4(1): 41-45.
    Bastiaens MT, Hoefnagel JJ, Vermeer BJ, Bavinck JNB, Bruijn JA, Westendorp RGJ. 1998. Differences in age, site distribution, and sex between nodular and superficial basal cell carcinomas indicate different types of tumors. Journal of Investigative Dermatology, 110(6): 880-884.
    Betti R, Radaelli G, Crosti C, Ghiozzi S, Moneghini L, Menni S. 2012.Margin involvement and clinical pattern of basal cell carcinoma with mixed histology. Journal of the European Academy of Dermatology and Venereology, 26(4): 483-487.
    Biernaskie JA, Mckenzie IA, Toma JG, Miller FD. 2007. Isolation of skinderived precursors (SKPs) and differentiation and enrichment of their Schwann cell progeny. Nature Protocols, 1(6): 2803-2812.
    Bonilla X, Parmentier L, King B, Bezrukov F, Kaya G, Zoete V, Seplyarskiy VB, Sharpe HJ, McKee T, Letourneau A, Ribaux PG, Popadin K, BassetSeguin N, Chaabene RB, Santoni FA, Andrianova MA, Guipponi M, Garieri M, Verdan C, Grosdemange K, Sumara O, Eilers M, Aifantis I, Michielin O, de Sauvage FJ, Antonarakis SE, Nikolaev SI. 2016. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nature Genetics, 48(4): 398-406.
    Burness CB. 2015. Sonidegib: first global approval. Drugs, 75(13): 1559-1566.
    Chen BZ, Trang V, Lee A, Williams NS, Wilson AN, Epstein EH, Jr., Tang JY, Kim J. 2016. Posaconazole, a second-generation triazole antifungal drug, inhibits the hedgehog signaling pathway and progression of basal cell carcinoma. Molecular Cancer Therapeutics, 15(5): 866-876.
    Chen JG, Fleischer AB, Jr., Smith ED, Kancler C, Goldman ND, Williford PM, Feldman SR. 2001. Cost of nonmelanoma skin cancer treatment in the United States. Dermatologic Surgery, 27(12): 1035-1038.
    Chen YB, Sasai N, Ma GQ, Yue T, Jia JH, Briscoe J, Jiang J. 2011. Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of smoothened. PLoS Biology, 9(6):e1001083.
    Chen YB, Jiang J. 2013. Decoding the phosphorylation code in Hedgehog signal transduction. Cell Research, 23(2): 186-200.
    Chen YH, Wang YH, Yu TH, Wu HJ, Pai CW. 2009. Transgenic zebrafish line with over- of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds. Transgenic Research, 18(6): 855-864.
    Christenson LJ, Borrowman TA, Vachon CM, Tollefson MM, Otley CC, Weaver AL, Roenigk RK. 2005. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA, 294(6): 681-690.
    de Giorgi V, Salvini C, Massi D, Raspollini MR, Carli P. 2005. Vulvar basal cell carcinoma: retrospective study and review of literature. Gynecologic Oncology, 97(1): 192-194.
    de Giorgi V, Massi D, Lotti T. 2006. Basal-cell carcinoma. The New England Journal of Medicine, 354(7): 769-771.
    De Zwaan SE, Haass NK. 2010. Genetics of basal cell carcinoma.Australasian Journal of Dermatology, 51(2): 81-92.
    Demers AA, Nugent Z, Mihalcioiu C, Wiseman MC, Kliewer EV. 2005.Trends of nonmelanoma skin cancer from 1960 through 2000 in a Canadian population. Journal of the American Academy of Dermatology, 53(2): 320-328.
    Dlugosz A, Agrawal S, Kirkpatrick P. 2012. Vismodegib. Nature Reviews Drug Discovery, 11(6): 437-438.
    Elliot OS, Elliot MW, Lisco H. 1966. Breast cancer in a tree shrew (Tupaia glis). Nature, 211(5053): 1105.
    Endo H, Mifune H, Maeda S, Kimura J, Yamada J, Rerkamnuaychoke W, Chungsamarnyart N, Ogawa K, Kurohmaru M, Hayashi Y. 1997. Cardiaclike musculature of the intrapulmonary venous wall of the long-clawed shrew (Sorex unguiculatus), common tree shrew (Tupaia glis) and common marmoset (Callithrix jacchus). Anatomical Record-advances in Integrative Anatomy & Evolutionary Biology, 247(1): 46-52.
    Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, Jiang XT, Lai R, Lang YS, Liang B, Liao SG, Mu D, Ma YY, Niu YY, Sun XQ, Xia JQ, Xiao J, Xiong ZQ, Xu L, Yang L, Zhang Y, Zhao W, Zhao XD, Zheng YT, Zhou JM, Zhu YB, Zhang GJ, Wang J, Yao YG. 2013.Genome of the Chinese tree shrew. Nature Communications, 4: 1426.
    Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkühler C, Pazzaglia S. 2016. MK-4101, a Potent inhibitor of the hedgehog pathway, is highly active against medulloblastoma and basal cell carcinoma. Molecular Cancer Therapeutics, 15(6): 1177-1189.
    Fuchs E. 2005. Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder. CNS Spectrums, 10(3): 182-190.
    Ge GZ, Xia HJ, He BL, Zhang HL, Liu WJ, Shao M, Wang CY, Xiao J, Ge F, Li FB, Chen CS. 2016. Generation and characterization of a breast carcinoma model by PyMT over in mammary epithelial cells of tree shrew, an animal close to primates in evolution. International Journal of Cancer, 138(3): 642-651.
    Ghaderi R, Haghighi F. 2005. Immunohistochemistry assessment of p53 protein in Basal cell carcinoma. Iranian journal of Allergy, Asthma and Immunology, 4(4): 167-171.
    Giorgi VD, Salvini C, Massi D, Raspollini MR, Carli P. 2005. Vulvar basal cell carcinoma: retrospective study and review of literature. Gynecologic Oncology, 97(1): 192-194.
    Graham RA, Lum BL, Cheeti S, Jin JY, Jorga K, Von Hoff DD, Rudin CM, Reddy JC, Low JA, Lorusso PM. 2011. Pharmacokinetics of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding.Clinical cancer research : an official journal of the American Association for Cancer Research, 17(8): 2512-2520.
    Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, Russell TL, Ellenbogen RG, Bernstein ID, Beachy PA, Olson JM. 2004. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Research, 64(21): 7794-7800.
    He BL, Xia HJ, Jiao JL, Wang CY, Zhang HL. 2016. Pathological analysis of the induced breast tumor models in tree shrew. Chinese Journal of Comparative Medicine, 26(3): 6-10. (in Chinese)
    Hertzler-Schaefer K, Mathew G, Somani AK, Tholpady S, Kadakia MP, Chen YP, Spandau DF, Zhang X. 2014. Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. Cell Reports, 6(5): 818-826.
    Hutchin ME, Kariapper MST, Grachtchouk M, Wang AQ, Wei LB, Cummings D, Liu JH, Michael LE, Glick A, Dlugosz AA. 2005. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation an
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (743) PDF downloads(461) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint