PMID- 7720642 OWN - NLM STAT- MEDLINE DCOM- 19950523 LR - 20061115 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 136 IP - 5 DP - 1995 May TI - Tumor-stroma interactions and stromal cell density regulate hepatocyte growth factor protein levels: a role for transforming growth factor-beta activation. PG - 1945-53 AB - Hepatocyte growth factor/scatter factor (HGF/SF), a fibroblast-derived mediator of epithelial and endothelial growth and motility, is regulated by factors present in media conditioned by breast tumor cell lines. Both inhibitory and stimulatory effects were observed dependent on culture conditions. The present work shows that breast tumor cell conditioned medium contains a latent HGF/SF inhibitory activity, which can be activated by a variety of treatments known to activate latent transforming growth factor-beta. Using blocking antibodies and other criteria, we show that transforming growth factor-beta present in epithelial cell conditioned medium is primarily responsible for mediating the down-regulation of fibroblast HGF/SF. Epithelial cell conditioned medium also contains a trypsin-sensitive and heat-stable stimulatory activity. Stromal cell density but not proliferation rate markedly alters HGF/SF expression. These results indicate that the expression of at least one epithelial morphogen, HGF/SF, is interdependently regulated by mesenchymal condensation and by factors released by neighboring epithelial and carcinoma cells. FAU - Seslar, S AU - Seslar S AD - Department of Cell Biology, Georgetown University Medical Center, Washington, D.C. 20007, USA. FAU - Nakamura, T AU - Nakamura T FAU - Byers, S AU - Byers S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Antibodies) RN - 0 (Culture Media, Conditioned) RN - 0 (Transforming Growth Factor beta) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 3.4.21.4 (Trypsin) SB - IM MH - Antibodies/pharmacology MH - Breast Neoplasms MH - Cell Communication MH - Cell Division MH - Cell Line MH - Culture Media, Conditioned MH - Enzyme-Linked Immunosorbent Assay MH - Epithelial Cells MH - Epithelium/physiology MH - Fetus MH - Hepatocyte Growth Factor/analysis/*biosynthesis/pharmacology MH - Humans MH - Kinetics MH - Lung MH - Temperature MH - Transforming Growth Factor beta/immunology/*physiology MH - Trypsin/pharmacology MH - Tumor Cells, Cultured EDAT- 1995/05/01 00:00 MHDA- 1995/05/01 00:01 CRDT- 1995/05/01 00:00 PHST- 1995/05/01 00:00 [pubmed] PHST- 1995/05/01 00:01 [medline] PHST- 1995/05/01 00:00 [entrez] AID - 10.1210/endo.136.5.7720642 [doi] PST - ppublish SO - Endocrinology. 1995 May;136(5):1945-53. doi: 10.1210/endo.136.5.7720642.