[Regulation of tumor metastasis and invasion by fibroblasts]

Using immunodeficient mice human tumor cell lines, which metastasize to specific organs from orthotopic implantation sites but not from ectopic sites, have been established. We have been studying mechanisms of the regulation of tumor metastasis by organ specific microenvironments, and have recently found significant differences in interactions between metastatic tumor cells and fibroblasts from different tissues. Fibroblasts isolated from orthotopic organ tissues of nude mice enhanced invasion of metastatic human colon carcinoma cells. In contrast, fibroblasts derived from a subcutaneous tissue suppressed carcinoma cell invasion. These divergent effects were found in part due to differential expression of cytokines and growth factors by fibroblasts from different tissues.