TY - JOUR
T1 - Characterization of an animal model of metastatic colon carcinoma
AU - Dunnington, Damien J.
AU - Buscarino, Charles
AU - Gennaro, Doris
AU - Greig, Russell
AU - Poste, George
PY - 1987/2/15
Y1 - 1987/2/15
N2 - Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The KI2/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD‐IX rat strain. Transmission electron microscopy of KI2/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of KI2/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19‐9 antigens by KI2/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). KI2/TR cells produced tumors following s.c. injection into syngeneic BD‐IX rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD‐IX rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of KI2/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the KI2/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.
AB - Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The KI2/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD‐IX rat strain. Transmission electron microscopy of KI2/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of KI2/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19‐9 antigens by KI2/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). KI2/TR cells produced tumors following s.c. injection into syngeneic BD‐IX rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD‐IX rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of KI2/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the KI2/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.
UR - http://www.scopus.com/inward/record.url?scp=0023124153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023124153&partnerID=8YFLogxK
U2 - 10.1002/ijc.2910390221
DO - 10.1002/ijc.2910390221
M3 - Article
C2 - 3804494
AN - SCOPUS:0023124153
SN - 0020-7136
VL - 39
SP - 248
EP - 254
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -