Orthotopic Models

Preclinical models of orthotopic tumors can better recapitulate the tumor microenvironment (TME)

While many CDX and PDX tumors grow subcutaneously in mice, sometimes a tumor model requires a specific kind of tumor microenvironment that can only be well recapitulated in the stroma of the primary organ. For example, hepatocellular carcinoma (HCC) liver cancer growing in liver are very well vascularized in comparison with HCC tumors growing subcutaneously, which might affect drug exposure and assumptions about metabolites. HCC is therefore a tumor type likely to benefit from orthotopic modeling. Bladder tumors at a primary tumor site contact urine and are subject to mechanical stress in a way that subcutaneous tumors do not, so orthotopic modeling of bladder cancer might be beneficial beyond SC modeling as well.Oncodesign Services can manage up to 80 animals/day in orthotopic surgery and about the same number for in vivo imaging timepoints. MRI is typically used to size tumors for randomization and sometimes to track tumor growth.Orthotopic modeling requires in vivo imaging. Oncodesign has numerous in vivo imaging platforms, including MRI, PET, PET/MRI, SPECT and optical imaging to monitor tumor volume and pharmacological biomarkers.

 

Orthotopic models list:

NameOrganHistological typeHost rodent species
SYNGENEIC
4T1BreastCarcinoma transitionalBalb/c Mouse
AY27BladderCarcinomaF344 Ficher Rat
C6BrainGliomaNude Rat
C6BrainGliomaWistar Rat
CT26ColonCarcinomaBalb/c Mouse
EMT6BreastMammary CarcinomaBalb/c Mouse
GS-9LBrainGliosarcomaF344 Ficher Rat
GV1A1BrainGliomaBDIX Rat
Hepa1-6LiverHepatocarcinomaC57BI/6 Mouse
MBT-2BladderCarcinomaC3H Mouse
MBT-IIBladderTumorWistar Rat
NCTC 2472BoneSarcomaC3H Mouse
R3327HProstateAdenocarcinomaCopenhagen Rat
RencaKidneyCarcinomaBalb/c Mouse
HUMAN CDX
LS 174TColonColorectal AdenocarcinomaNude Rat
MDA-MB-175BreastAdenocarcinomaNOD SCID Mouse
NCI-H146Lungcarcinoma-SCLCNude Rat
NCI-H209LungCarcinoma SCLCNude Rat
NCI-H460LungCarcinoma-NSCLCSwiss Nude Mouse
NIH:OVCAR-3OvaryAdenocarcinomaNude Rat
PANC-1PancreasCarcinomaNude Rat
PC-3ProstateAdenocarcinomaNude Rat
PC-3-MM2ProstateAdenocarcinomaNude Rat
RT-4 (CVE-4)BladderTransitional papillomaNude Rat
SK-BR-3BreastAdenocarcinoma colorectalNOD SCID Mouse
SW-620ColonAdenocarcinomacb17 SCID Mouse
U-87 MGBrainGlioblastomaNude Rat
U-87 MGBrainGlioblastomaSwiss Nude Mouse
U-87 MGBrainGlioblastomaNMRI Nude Mouse

Model example #1

The GL261 syngeneic mouse glioma model was injected orthotopically in the brains of mice.  The tumors were detected 8 days after implantation, by MRI.  The tumors were quantifiable with adequate animal health metrics for at least 15 days, with survival dropping after day 20.

Orthotopic - GL261 orthotopic glioma model

Model example #2

The 4T1 mouse mammary carcinoma model was injected into the mammary fat pad (MFP) in BALB/c mice.  Tumor size was measured by caliper and total tumor burden was counted after termination.  Indomethacin suppressed tumor growth a little, and halved the number of detectable lung metastases.

MetastaticModels - 4T1 breast to lung mets