Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.
Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.
Yasui
N
N
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Sakamoto
M
M
Ochiai
A
A
Ino
Y
Y
Akimoto
S
S
Orikasa
A
A
Kitajima
M
M
Hirohashi
S
S
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000032:analysis / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000378:metabolism; D015197:Carcinogenicity Tests; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000032:analysis / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000637:transplantation
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D066246:ErbB Receptors