PMID- 10399964 OWN - NLM STAT- MEDLINE DCOM- 19990727 LR - 20190708 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 82 IP - 3 DP - 1999 Jul 30 TI - Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-beta1. PG - 449-58 AB - Carcinoma cells frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration." We have previously presented an in vitro two-dimensional cohort migration model, in which highly metastatic variant L-10 cells of human rectal adenocarcinoma cell line RCM-1 moved as coherent cell sheets when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor/scatter factor (HGF/SF). Pericellular deposition of EDA-containing fibronectin (EDA+FN) was essential for TPA-induced cohort migration. In this study, we investigated how colon-derived fibroblasts could affect the induction of cohort migration of colorectal carcinoma cells by HGF/SF, since carcinoma cell-fibroblast interactions frequently regulate biological events during cancer cell invasion. Fibroblasts co-cultured with L-10 carcinoma cells stimulated HGF/SF-induced cohort migration of L-10 cells up to 2 to 3-fold. Conditioned medium (CM) from fibroblasts that were cultured alone was not effective but CM from fibroblasts cocultured with carcinoma cells enhanced HGF/SF-induced cohort migration, and this effect in CM was found to be mediated by TGF-beta1 upregulated in co-cultured conditions. Among the motogenic growth factors examined, only TGF-beta1 synergistically stimulated HGF/SF-induced L-10 cell cohort migration, although TGF-beta1 alone did not induce cohort migration. TGF-beta1 also exhibited synergistic effect in several other human colorectal carcinoma cell lines. The synergistic stimulation of L-10 cell cohort migration by HGF/SF and TGF-beta1 was associated with increased production of motility-enhancing EDA+FN by L-10 cells, and blocking FN with a specific antibody effectively inhibited the synergistic effect. FAU - Shimao, Y AU - Shimao Y AD - Department of Pathology, Miyazaki Medical College, Kiyotake, Japan. FAU - Nabeshima, K AU - Nabeshima K FAU - Inoue, T AU - Inoue T FAU - Koono, M AU - Koono M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Fibronectins) RN - 0 (Recombinant Proteins) RN - 0 (Transforming Growth Factor beta) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Adenocarcinoma/*pathology MH - Cell Movement/drug effects MH - Colorectal Neoplasms/*pathology MH - Drug Synergism MH - Fibroblasts/drug effects MH - Fibronectins/*biosynthesis MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Neoplasm Invasiveness MH - Recombinant Proteins/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stimulation, Chemical MH - Transforming Growth Factor beta/*pharmacology MH - Tumor Cells, Cultured MH - Up-Regulation EDAT- 1999/07/10 10:00 MHDA- 2000/06/20 09:00 CRDT- 1999/07/10 10:00 PHST- 1999/07/10 10:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/07/10 10:00 [entrez] AID - 10.1002/(SICI)1097-0215(19990730)82:3<449::AID-IJC20>3.0.CO;2-H [pii] AID - 10.1002/(sici)1097-0215(19990730)82:3<449::aid-ijc20>3.0.co;2-h [doi] PST - ppublish SO - Int J Cancer. 1999 Jul 30;82(3):449-58. doi: 10.1002/(sici)1097-0215(19990730)82:3<449::aid-ijc20>3.0.co;2-h.