Table 2.
Transplantation models of colorectal cancer (CRC)
| Transplantation model | Strengths | Weaknesses |
|---|---|---|
| Subcutaneous CRC cell line xenograft: injection of cells e.g. HCT116 and HT29 to immune deficient mouse | • Low cost | • Representative of advanced disease |
| • Rapid tumour growth (2 weeks) | • Have undergone significant clonal selection 73 | |
| • Well characterized cell‐lines: gene mutation status, transcriptome and drug response data available 73, 106, 107 | • Microenvironmental differences (cells derived from colorectum injected under skin) | |
| • Easy to genetically manipulate prior to transplantation e.g. with inducible shRNA or by CRISPR/Cas9 108 | • Species mismatch in tumour (human) and stromal (mouse) cell may limit cross‐talk | |
| • Model accessible to the majority of research labs | • Immune deficient host | |
| • Rarely metastasise | ||
| Orthotopic xenografts of CRC cell lines: injection of cells into intestinal serosa of immune deficient mouse | • As above | • As above (except for ‘rarely metastasise’) |
| • More natural microenvironment for CRC cells | • May require surgery to implant cells | |
| • Some metastasise to liver e.g. from HCT116 or HT29 | ||
| Patient‐derived xenografts (PDXs): Suturing of 1–2 mm fragments of fresh surgical specimens of CRC, to intestine of immune deficient mouse | • Reproducible liver metastasis | • Not readily scalable |
| • Avoid selection of dominant clones during long‐term cell culture | • Host (mouse) stromal cells replace human stromal cells within a few weeks (species mismatch) | |
| • Temporary preservation of species‐specific tumour‐stromal cell cross talk | • Immune deficient host | |
| • More natural microenvironment for CRC cells | • Limited by availability of surgical specimens | |
| • Expensive (labour intensive and time consuming) | ||
| Syngraft/Isograft: Suturing 1–2 mm mouse tumour fragments or mouse tumour cell lines e.g. MC38 cells to a genetically identical inbred, immune competent mouse | • No species mismatch between tumour and stromal cells | • Expensive (labour intensive and time consuming) |
| • Host has intact immune system that enables testing of immunomodulatory anti‐cancer agents | • The model is not human |