CONSISTENT HEPATIC METASTASIS OF HUMAN COLORECTAL-CANCER IN SEVERE COMBINED IMMUNODEFICIENT MICE

A major stumbling block in the study of human colorectal cancer metast asis has been the lack of an effective in vivo model producing liver m etastasis on a consistent basis. In this study surgical specimens of c olorectal carcinoma were implanted in scid mice and studied for engraf tment, growth, and the capacity to produce hepatic metastases. Human c olorectal cancers would engraft and propagate in the subcutis and intr aperitoneally. Sporadic metastasis to the liver occurred in 3 of 54 (6 %) animals with cancer implanted subcutaneously. Liver metastasis occu rred in 24 of 25 (96%) mice with cancer implanted in the gonad fat pad . Tumor growth to extremely large volumes subcutaneously did not enhan ce metastatic potential, and neither did longer term growth in the sub cutaneous space. Tumor placed in the gonad fat required no special man ipulation and in most cases a single piece of solid tumor was implante d. In situ hybridization confirmed the persistence of the human tissue in these metastasizing tumors. Our model will allow for the study of the processes involved in metastasis of solid tumors, characterization of differences between the primary tumor and the metastatic one, and evaluation of possible therapeutic modalities. (C) 1996 Academic Press , Inc.