Tumor cell dissemination in a human colon cancer animal model: orthotopic implantation or intraportal injection?
BACKGROUND
The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination of tumor cells.


METHODS
To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 x 10(6) HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow.


RESULTS
Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 x 10(6) HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 x 10(6) cells also generated MRD in the bone marrow in 63% of animals.


CONCLUSIONS
The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.
Thalheimer
A
A
Department of Surgery, University of Wurzburg Hospital, Wurzburg, Germany. thalheimer_a@chirurgie.uni-wuerzburg.de
Otto
C
C
Bueter
M
M
Illert
B
B
Gattenlohner
S
S
Gasser
M
M
Fein
M
M
Germer
C T
CT
Waaga-Gasser
A-M
AM
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D004195:Disease Models, Animal; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007275:Injections, Intravenous; D053554:Keratin-20 / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods; D009360:Neoplastic Cells, Circulating; D011169:Portal Vein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
D053554:Keratin-20