title: Human peri-tumoral and lung fibroblasts produce paracrine motility factors for recently established human sarcoma cell strains.
abstract: 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-I 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.
authors.affiliation: Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: R E
authors.initials: RE
authors.lastname: Pollock
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: G L
authors.initials: GL
authors.lastname: Nicolson
mesh_terms: D001483:Base Sequence; D002465:Cell Movement; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology*; D008175:Lung Neoplasms / Q000556:secondary; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012509:Sarcoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D005353:Fibronectins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C107678:fibroblast motility-stimulating factor; D017228:Hepatocyte Growth Factor