An orthotopic mouse model of remetastasis of human colon cancer liver metastasis

Whether liver metastases from colon cancer are capable of metastasizing to other sites is an important question in surgical oncology. To answer this q uestion, we have developed a highly metastatic orthotopic transplant model of a liver metastasis from a human colon cancer patient in nude mice that t argets the liver and lymph nodes. The metastatic human tumor was transplant ed in athymic nude mice by surgical orthotopic implantation (SOI) of a live r metastasis from a colon cancer patient. The human colon tumor was then su bsequently implanted in the colon by SOI or, in an additional series of nud e mice, in the liver by surgical hepatic implantation (SHI). The mice were then explored over time for lymph node involvement beginning 10 days after implantation. After SOI, 100% of the animals had liver metastasis within 10 days, and subsequently, 19 days after SOI, all lymph nodes draining the li ver were involved with metastasis without any retroperitoneal or lung tissu e involvement, After SHI, all sites of lymphatic drainage of the Liver, inc luding portal, celiac, and mediastinal lymph nodes, mere massively involved by metastasis in 100% of the animals as early as 10 days after tumor impla ntation on the li, er. The results of this study demonstrate that liver met astases from colon cancer are capable of remetastasizing to other sites. Th is study thus suggests that in colon cancer patients with liver metastasis, mediastinal, celiac, and portal lymph node metastases originate from the l iver metastasis and not, as previously thought, from primary colon cancer.