Construction of orthotopic xenograft mouse models for human pancreatic cancer

Dai,Lei; Lu,Caide; Yu,Xi; Dai,Long‑Jun; Zhou,Jeff X.

doi:10.3892/etm.2015.2642

Construction of orthotopic xenograft mouse models for human pancreatic cancer

Authors:
- Lei Dai
- Caide Lu
- Xi Yu
- Long‑Jun Dai
- Jeff X. Zhou
View Affiliations

Affiliations: Department of Pathology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital, Ningbo, Zhejiang 315040, P.R. China, Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC V5Z IL8, Canada
Published online on: July 16, 2015 https://doi.org/10.3892/etm.2015.2642
Pages: 1033-1038

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Animal models are indispensable for the study of tumorigenesis and the development of anti‑cancer drugs for human pancreatic cancer. In the present study, two orthotopic xenograft mouse models were developed. AsPC‑1 human pancreatic cancer cells were stably labeled with red fluorescent protein (RFP) and injected subcutaneously into nude mice. For the orthotopic tumor mass model, the formed subcutaneous tumors were cut into blocks and implanted into the pancreas of nude mice via laparotomy. For the Matrigel™ tumor block model, solidified Matrigel containing RFP‑labeled AsPC‑1 cells was cut into blocks and implanted into the pancreas of nude mice. A subcutaneous tumor xenograft model was used as a control. Tumor growth and metastasis were assessed using an in vivo fluorescence imaging system. Thirty‑six days after implantation, all mice from the two orthotopic xenograft models (n=20 per group) and 55% of the subcutaneous xenograft mice (n=20) developed tumors. The tumor growth rate was significantly higher in the orthotopic models than that in the subcutaneous model (P<0.01). Metastasis to organs such as the liver was observed in the orthotopic tumor models. Histological examination showed that the tumors were poorly differentiated adenocarcinomas. In conclusion, two orthotopic xenograft mouse models of human pancreatic cancer were established; these exhibited greater tumor growth and metastasis than the subcutaneous xenograft mouse model.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
2	Brennan MF: Adjuvant therapy following resection for pancreatic adenocarcinoma. Surg Oncol Clin N Am. 13:555–566. 2004. View Article : Google Scholar : PubMed/NCBI
3	Stojadinovic A, Hoos A, Brennan MF and Conlon KC: Randomized clinical trials in pancreatic cancer. Surg Oncol Clin N Am. 11:207–229. 2002. View Article : Google Scholar : PubMed/NCBI
4	Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK and Hruban RH: Recent progress in pancreatic cancer. CA Cancer J Clin. 63:318–348. 2013. View Article : Google Scholar : PubMed/NCBI
5	Yamamura K, Kasuya H, Sahin TT, Tan G, Hotta Y, Tsurumaru N, Fukuda S, Kanda M, Kobayashi D, Tanaka C, et al: Combination treatment of human pancreatic cancer xenograft models with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib and oncolytic herpes simplex virus HF10. Ann Surg Oncol. 21:691–698. 2014. View Article : Google Scholar : PubMed/NCBI
6	Nikfarjam M, Yeo D, He H, Baldwin G, Fifis T, Costa P, Tan B, Yang E, Wen S and Christophi C: Comparison of two syngeneic orthotopic murine models of pancreatic adenocarcinoma. J Invest Surg. 26:352–359. 2013. View Article : Google Scholar : PubMed/NCBI
7	Troiani T, Schettino C, Martinelli E, Morgillo F, Tortora G and Ciardiello F: The use of xenograft models for the selection of cancer treatments with the EGFR as an example. Crit Rev Oncol Hematol. 65:200–211. 2008. View Article : Google Scholar : PubMed/NCBI
8	Bimonte S, Barbieri A, Palma G, Luciano A, Rea D and Arra C: Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. BioMed Res Int. 2013:8104232013. View Article : Google Scholar : PubMed/NCBI
9	Nangami GN, Watson K, Parker Johnson K, Okereke KO, Sakwe A, Thompson P, Frimpong N and Ochieng J: Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel. Biochem Biophys Res Commun. 438:660–665. 2013. View Article : Google Scholar : PubMed/NCBI
10	Büchler P, Reber HA, Roth MM, Shiroishi M, Friess H and Hines OJ: Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer. Neoplasia. 9:119–127. 2007. View Article : Google Scholar : PubMed/NCBI
11	Hakkarainen T, Särkioja M, Lehenkari P, Miettinen S, Ylikomi T, Suuronen R, Desmond RA, Kanerva A and Hemminki A: Human mesenchymal stem cells lack tumor tropism but enhance the antitumor activity of oncolytic adenoviruses in orthotopic lung and breast tumors. Hum Gene Ther. 18:627–641. 2007. View Article : Google Scholar : PubMed/NCBI
12	Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D and Catalano P: Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: A trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 27:3778–3785. 2009. View Article : Google Scholar : PubMed/NCBI
13	McAllister SS and Weinberg RA: Tumor-host interactions: A far-reaching relationship. J Clin Oncol. 28:4022–4028. 2010. View Article : Google Scholar : PubMed/NCBI
14	Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, et al: Gruppo Oncologico Italia Meridionale (GOIM); Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD); Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC): Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: The GIP-1 study. J Clin Oncol. 28:1645–1651. 2010. View Article : Google Scholar : PubMed/NCBI
15	Cui L, Chen P, Tan Z, Li W and Dong Z: Hemostatic gelatin sponge is a superior matrix to matrigel for establishment of LNCaP human prostate cancer in nude mice. Prostate. 72:1669–1677. 2012. View Article : Google Scholar : PubMed/NCBI