Table 1.
Proposed model | Existing models | ||||
---|---|---|---|---|---|
STIM | Genetically engineered KPC8 | KPC cell line implantation Model4,23 | Human PDAC cell line xenograft23 | Patient derived tumor xenograft (PDX)19 | |
Mouse genetic background | C57BL/6J (wild type) | C57BL/6J (wild type) | C57BL/6J (wild type) | Athymic/SCID/NSG | Athymic/SCID/NSG |
Immune background | Immunocompetent | Immunocompetent | Immunocompetent | Immunodeficient (lacks functional adaptive immunity) | Immunodeficient (lacks functional adaptive immunity) |
Mutation profile | Mutations present only in implanted tumor tissue | Mutations present throughout pancreas | Mutations present only in implanted cells | Mutations present only in implanted cells | Mutations present only in implanted tumor tissue |
Species | Mouse tumor | Mouse tumor | Mouse cell line | Human cell lines | Human tumor |
Stromal content | High stromal content (ECM, fibroblasts and activated stellate cells) | High stromal content (ECM, fibroblasts and activated stellate cells) | Low stromal content | Absent stroma | High stromal content (ECM, fibroblasts and activated stellate cells) |
Variability | Less variability in time to invasive disease ( within 2 weeks) | High variability in time to invasive disease (Range, 47–355 days) | Less variability in time to invasive disease (within 2 weeks) | Less variability in time to invasive disease (2–3 weeks); depends on cell line | Variability in time to tumor development (2–12 months ); depends on primary tumor |
Predictability | Predictable course of disease progression | Unpredictable course of disease progression | Predictable course of disease progression | Predictable course of disease progression | Predictable course of disease progression and variable engraftment rates (23–75%) |
Tumor milieu | Tumor growth is in natural milieu (pancreas) | Tumor growth is in natural milieu (pancreas) | Tumor growth is in natural milieu (pancreas) | Tumor growth is in unnatural (subcutaneous) milieu or natural (orthotopic) milieu | Tumor growth is in unnatural (subcutaneous) milieu or natural (orthotopic) milieu |
Metastatic disease | Metastatic and loco-regional disease present after 2 months of implantation | Metastatic and loco-regional disease develops at variable time. | Metastatic and loco-regional disease present, but concerns of confounding due to cell spillage during orthotopic implantation | Metastatic and loco-regional disease absent in subcutaneous models and present in orthotopic. | Metastatic and loco-regional disease absent in subcutaneous models and present in orthotopic. |
Tumor pathology | Well differentiated to poorly differentiated tumors (depends on parent tumor) | Well differentiated to poorly differentiated tumors | Poorly differentiated tumors | Variable | Variable |
Tumor microenvironment | Robust desmoplastic reaction, collagen and vimentin content, immune infiltration, and stellate cells | Robust desmoplastic reaction, collagen and vimentin content, immune infiltration, and stellate cells | Paucity of desmoplastic reaction, less collagen, vimentin and stellate cells, and less immune infiltration | Paucity of desmoplastic reaction as well as infiltrating immune cells | Robust desmoplastic reaction without infiltrating adaptive immune cells |
Surrounding pancreas | Adjacent normal/wild type pancreas | Adjacent mutant Kras-p53 pancreas | Adjacent normal/wild type pancreas | No surrounding pancreatic tissue (subcutaneous) or adjacent immunodeficient pancreas (orthotopic) | No surrounding pancreatic tissue (subcutaneous) or adjacent immunodeficient pancreas (orthotopic) |
STIM: Syngeneic Tumor Implanta3on Model; SCID: Severe combined immunodeficiency; NSG: Non-obese diabe3c (NOD) SCID gamma mice; ECM: Extracellular matrix STIM Syngeneic Tumor Implantation Model, SCID severe combined immunodeficiency, NSG non-obese diabetic (NOD) SCID gamma mice, ECM extracellular matrix