METASTATIC MODELS OF HUMAN CANCER XENOGRAFTED IN THE NUDE-MOUSE - THE IMPORTANCE OF ORTHOTOPIC TRANSPLANTATION

Metastatic model of human tumor xenografts have been developed using orthotopic transplantation of histologically intact tissue (onplantation) of lung, stomach, colon, pancreatic, prostate and bladder carcinomas. These models represent the entire process of the metastasis, consisting of local tumor growth, vascular and lymphatic invasion at the local site, flow in the vessels and lymphatic, extravasation at the metastatic organs, and seeding and growth at relevant metastatic sites. Orthotopically transplanted human small-cell lung carcinoma displayed a different chemosensitivity pattern compared with the subcutaneous transplanted model, suggesting different pharmacodynamics between the orthotopic lung and the ectopic subcutaneous sites. The intact-tissue orthotopic-onplantation model seems to be useful to study the mechanism of metastasis for discovery of antimetastatic agents and for the patient tumors and for this treatment design. (C) 1994 Wiley-Liss, Inc.