Patient-Derived Xenograft and Mice Models in Esophageal Squamous Cell Carcinoma

  • Alfred K. LamEmail author
  • Johnny C. TangEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2129)


Mouse models are important in the study of pathogenesis, testing new treatment, and monitoring the progress of treatment in patients with esophageal squamous cell carcinoma (ESCC). The mice commonly used are immunosuppressed. The first category of models is for basic research and includes genetically engineered mouse models and carcinogen- or diet-induced mouse models. The second category of models involves either injection of cells with altered gene function related to pathogenesis of ESCC or ESCC cell lines. This method is commonly used and relatively inexpensive and simple to use. These cells commonly being subcutaneous injected in flank (subcutaneous xenograft model), tail vein, or peritoneum of immunodeficient mice. Direct implantation into the esophagus (orthotopic xenograft model) is also performed despite the cost and technical difficulties. The third category of mouse model is the patient-derived xenograft (PDX) model. In this model, ESCC tissues (instead of cell lines) removed from the patient are implanted into immunodeficient mice. This model appears promising for personalized medicine and of high resemblance to the nature of human ESCC, but there are many limitations for the use. It is likely to be used more in research in ESCC in the future. In this chapter, we detailed the preparation and experiments of PDX model from a patient with ESCC.

Key words

ESCC Esophageal Squamous cell carcinoma Patient-derived xenograft Mice model 


  1. 1.
    Jung J, Seol HS, Chang S (2018) The generation and application of patient-derived xenograft model for cancer research. Cancer Res Treat 50:1–10CrossRefGoogle Scholar
  2. 2.
    Tang JC, Lam KY, Law S, Wong J, Srivastava G (2001) Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR. Clin Cancer Res 7:1539–1545PubMedGoogle Scholar
  3. 3.
    Law FB, Chen YW, Wong KY, Ying J, Tao Q, Langford C, Lee PY, Law S, Cheung RW, Chui CH, Tsao SW, Lam KY, Wong J, Srivastava G, Tang JC (2007) Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma. Oncogene 26:5877–5888CrossRefGoogle Scholar
  4. 4.
    Tang WK, Chui CH, Fatima S, Kok SH, Pak KC, Ou TM, Hui KS, Wong MM, Wong J, Law S, Tsao SW, Lam KY, Beh PS, Srivastava G, Chan AS, Ho KP, Tang JC (2007) Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma. Int J Mol Med 19:915–923PubMedGoogle Scholar
  5. 5.
    Fatima S, Chui CH, Tang WK, Hui KS, Au HW, Li WY, Wong MM, Cheung F, Tsao SW, Lam KY, Beh PS, Wong J, Law S, Srivastava G, Ho KP, Chan AS, Tang JC (2006) Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma. Int J Mol Med 17:159–170PubMedGoogle Scholar
  6. 6.
    Hu YC, Lam KY, Law SY, Wan TS, Ma ES, Kwong YL, Chan LC, Wong J, Srivastava G (2002) Establishment, characterization, karyotyping, and comparative genomic hybridization analysis of HKESC-2 and HKESC-3: two newly established human esophageal squamous cell carcinoma cell lines. Cancer Genet Cytogenet 135:120–127CrossRefGoogle Scholar
  7. 7.
    Tang JC, Wan TS, Wong N, Pang E, Lam KY, Law SY, Chow LM, Ma ES, Chan LC, Wong J, Srivastava G (2001) Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line SLMT-1 of Chinese origin. Cancer Genet Cytogenet 124:36–41CrossRefGoogle Scholar
  8. 8.
    Hu Y, Lam KY, Wan TS, Fang W, Ma ES, Chan LC, Srivastava G (2000) Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma. Cancer Genet Cytogenet 118:112–120CrossRefGoogle Scholar
  9. 9.
    Pun IH, Chan D, Chan SH, Chung PY, Zhou YY, Law S, Lam AK, Chui CH, Chan AS, Lam KH, Tang JC (2017) Anti-cancer effects of a novel quinoline derivative 83b1 on human esophageal squamous cell carcinoma through down-regulation of COX-2 mRNA and PGE(2). Cancer Res Treat 49:219–229CrossRefGoogle Scholar
  10. 10.
    Ip JC, Ko JM, Yu VZ, Chan KW, Lam AK, Law S, Tong DK, Lung ML (2015) A versatile orthotopic nude mouse model for study of esophageal squamous cell carcinoma. Biomed Res Int 2015:910715CrossRefGoogle Scholar
  11. 11.
    Ng HY, Li J, Tao L, Lam AK, Chan KW, Ko JMY, Yu VZ, Wong M, Li B, Lung ML (2018) Chemotherapeutic treatments increase PD-L1 expression in esophageal squamous cell carcinoma through EGFR/ERK activation. Transl Oncol 11:1323–1333CrossRefGoogle Scholar
  12. 12.
    Nishikawa T, Takaoka M, Ohara T, Tomono Y, Hao H, Bao X, Fukazawa T, Wang Z, Sakurama K, Fujiwara Y, Motoki T, Shirakawa Y, Yamatsuji T, Tanaka N, Fujiwara T, Naomoto Y (2013) Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice. Cancer Biol Ther 14:230–236CrossRefGoogle Scholar
  13. 13.
    Hou W, Qin X, Zhu X, Fei M, Liu P, Liu L, Moon H, Zhang P, Greshock J, Bachman KE, Ye BC, Wang H, Zang CY (2013) Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models. Oncol Rep 30:707–714CrossRefGoogle Scholar
  14. 14.
    Zhang J, Jiang D, Li X, Lv J, Xie L, Zheng L, Gavine PR, Hu Q, Shi Y, Tan L, Ge D, Xu S, Li L, Zhu L, Hou Y, Wang Q (2014) Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery. Lab Investig 94:917–926CrossRefGoogle Scholar
  15. 15.
    Wu X, Zhang J, Zhen R, Lv J, Zheng L, Su X, Zhu G, Gavine PR, Xu S, Lu S, Hou J, Liu Y, Xu C, Tan Y, Xie L, Yin X, He D, Ji Q, Hou Y, Ge D (2012) Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models. J Transl Med 10:180CrossRefGoogle Scholar
  16. 16.
    Xu C, Li X, Liu P, Li M, Luo F (2019) Patient-derived xenograft mouse models: a high fidelity tool for individualized medicine. Oncol Lett 17:3–10PubMedGoogle Scholar
  17. 17.
    Jirkof P, Tourvieille A, Cinelli P, Arras M (2015) Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation. Lab Anim 49:177–187CrossRefGoogle Scholar
  18. 18.
    Tomayko MM, Reynolds CP (1989) Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 24:148–154CrossRefGoogle Scholar
  19. 19.
    Vosgha H, Ariana A, Smith RA, Lam AK (2018) miR-205 targets angiogenesis and EMT concurrently in anaplastic thyroid carcinoma. Endocr Relat Cancer 25:323–337CrossRefGoogle Scholar
  20. 20.
    Maroof H, Islam F, Dong L, Ajjikuttira P, Gopalan V, McMillan NAJ, Lam AK (2018) Liposomal delivery of miR-34b-5p induced cancer cell death in thyroid carcinoma. Cell 7:E265CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Cancer Molecular Pathology, School of MedicineGriffith UniversityGold CoastAustralia
  2. 2.Kamford Health and Genetics CentreCentralHong Kong

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