Preservation of metastatic ability of colorectal tumor cells stratified by inducibility of endogenous tumor necrosis factor after orthotopic transplantation in nude mice.
BACKGROUND
Inducibility of endogenous tumor necrosis factor (TNF) by colorectal tumor cells can be regarded as a novel prognostic factor in terms of distant metastasis or local recurrence following curative operation, especially at Duke's stage C. In this study, the metastatic ability of human colorectal tumor cells stratified by inducibility of endogenous TNF was analyzed by orthotopic transplantation in nude mouse.


METHODS
Fifty three cases of freshly resected colorectal tumor specimens cut into about 50mg pieces were inoculated into the cecum wall of nude mice. Two to nine months after transplantation, tumor growth on this wall and metastases to the peritoneal wall as well as to the liver were assessed.


RESULTS
Of forty one evaluable cases, successful transplantation was observed in twenty nine (70%), and metastases to the peritoneal wall or to the liver was found in thirteen (32%), or eight cases (20%), respectively. In the twenty nine cases with local tumor growth, incidence of the liver metastases in nude mice when tumor specimens from patients with liver metastases (4/8) were used was significantly higher than that from patients without liver metastases (4/21) (P = 0.096). Inducibility of endogenous TNF was separately analyzed in fourteen of the evaluable twenty nine cases. Seven cases belonged to the high group and seven to the low group in terms of the amount of endogenous TNF secreted by tumor cells. Incidence of metastases in mice was 1/7 in the high group and 6/7 in the low group, and there was a statistically significant difference between liver metastases in mice and inducibility of endogenous TNF by colorectal tumor cells (p = 0.0057).


CONCLUSIONS
From these results, it is strongly suggested that inducibility of endogenous TNF by colorectal tumor cells can affect a patient's prognosis since it regulates metastatic ability to the liver.
Soma
G
G
Department of Molecular Medicine, Takano Hospital, Kumamoto, Japan.
Inagawa
H
H
Fukushima
Y
Y
Kanou
J
J
Tomita
K
K
Takano
M
M
Goto
S
S
Takagi
K
K
D000818:Animals; D003110:Colonic Neoplasms / Q000556:secondary; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000556:secondary; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha