HUMAN PERI-TUMORAL AND LUNG FIBROBLASTS PRODUCE PARACRINE MOTILITY FACTORS FOR RECENTLY ESTABLISHED HUMAN SARCOMA CELL STRAINS

Paracrine motogenic cytokines secreted by normal cells can stimulate metastatic cell invasion. For example, human fibroblasts secrete hepatocyte growth factor/scatter factor (HGF/SF), which stimulates paracrine migration of epithelial and certain carcinoma cells, and migration-stimulating factor (MSF), which stimulates autocrine migration of fibroblasts from certain breast carcinomas. We found that human peri-tumoral and lung fibroblasts secrete motility-stimulating activity for several recently established human sarcoma cell strains. Motility of lung metastasis-derived SYN-1 sarcoma cells was preferentially stimulated by human lung and peri-tumoral fibroblast motility-stimulating factors (FMSFs). FMSFs were non-dialyzable, susceptible to trypsin and sensitive to dithiothreitol. Cycloheximide inhibited accumulation of FMSF activity in conditioned medium; however, addition of cycloheximide to the migration assay did not significantly affect motility-stimulating activity. Purified HGF/SF, rabbit anti-hHGF and RT-PCR analysis of peri-tumoral and lung fibroblast HGF/SF mRNA expression indicated that FMSF activity was unrelated to HGF/SF. Partial purification of FMSF by gel exclusion chromatography revealed several peaks of activity, suggesting multiple FMSF molecules or complexes. Since human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), FMSF may play a role in this process independent of HGF/SF. (C) 1995 Wiley-Liss, Inc.