Development of orthotopic tumour models using ultrasound-guided intrahepatic injection

L E McVeigh, I Wijetunga, N Ingram, G Marston, R Prasad, A F Markham, P L Coletta

Research output: Contribution to journalArticlepeer-review

Abstract

Mouse models of human diseases are an essential part of the translational pipeline. Orthotopic tumour mouse models are increasingly being used in cancer research due to their increased clinical relevance over subcutaneous xenograft models, particularly in relation to metastatic disease. In this study, we have developed orthotopic colorectal cancer liver metastases (CRCLM) and primary cholangiocarcinoma (CCA) models in BALB/c nude mice using minimally invasive ultrasound-guided intrahepatic injection. Due to its minimally invasive nature, the method reduced risk from surgical complications whilst being fast and easy to perform and resulted in measurable tumour volumes 1 to 3 weeks post-injection. Tumour volumes were monitored in vivo by weekly high-frequency ultrasound (HF-US) and/or twice weekly bioluminescence imaging (BLI) and confirmed with end-point histology. Take rates were high for human CRC cells (>73%) and for CCA cells (90%). We have demonstrated that this method reliably induces CRCLM and CCAs, in which tumour volume can be monitored throughout using HF-US and/or BLI. This provides a promising experimental tool for future testing of cancer therapeutics in an orthotopic model.

Original languageEnglish
Pages (from-to)9904
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 9 Jul 2019

Keywords

  • Animals
  • Colorectal Neoplasms/diagnostic imaging
  • Disease Models, Animal
  • Female
  • Humans
  • Liver Neoplasms/diagnostic imaging
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Burden
  • Tumor Cells, Cultured
  • Ultrasonography/methods
  • Xenograft Model Antitumor Assays

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