PMID- 8306528 OWN - NLM STAT- MEDLINE DCOM- 19940317 LR - 20191023 IS - 0262-0898 (Print) IS - 0262-0898 (Linking) VI - 12 IP - 2 DP - 1994 Mar TI - Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line. PG - 143-54 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose pleiotropic effects on epithelial cells include the stimulation of motility, mitosis and tubulogenesis. These responses are mediated by the cell surface tyrosine kinase receptor c-met. Because both the cytokine and receptor are found in the gastrointestinal tract, we have studied the effects of HGF/SF on transformed gut epithelial cells which express c-met. Here we describe the response of a new transformed human jejunal epithelioid cell line (HIE-7) to HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2, Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and protein. In addition, electron microscopic analysis revealed the presence of primitive junctions and rudimentary microvilli, but features of polarization were absent. When grown on reconstituted basement membranes, HIE-7 cells formed closely associated multicellular cord-like structures adjacent to acellular spaces. However, the cells did not mature structurally, form lumen-like structures or express disaccharidase mRNA, even in the presence of recombinant HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated their rapid migration in a modified wound assay. To determine whether the mitogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across reconstituted basement membranes, a Boyden chamber chemoinvasion assay was performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that crossed the basement membrane barrier, while only stimulating a small increase in chemotaxis across a collagen IV matrix, suggesting that the cytokine activates matrix penetration by these cells. rHGF also stimulated the invasion of basement membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948). In contrast, two moderately well differentiated colon cancer cell lines (Caco-2 and HT-29) did not manifest an invasive response when exposed to rHGF. These results suggest that HGF/SF may play a significant role in the invasive behavior of anaplastic and poorly differentiated gut epithelial tumors. FAU - Sunitha, I AU - Sunitha I AD - Department of Pathology, Georgetown University School of Medicine, Washington 20007. FAU - Meighen, D L AU - Meighen DL FAU - Hartman, D P AU - Hartman DP FAU - Thompson, E W AU - Thompson EW FAU - Byers, S W AU - Byers SW FAU - Avigan, M I AU - Avigan MI LA - eng GR - NCI CA54818/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Clin Exp Metastasis JT - Clinical & experimental metastasis JID - 8409970 RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Base Sequence MH - Basement Membrane/*drug effects MH - Cell Line, Transformed MH - Chemotaxis MH - Colonic Neoplasms/pathology MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Jejunum/cytology/*drug effects/metabolism MH - Molecular Sequence Data MH - *Neoplasm Invasiveness MH - Proto-Oncogene Proteins c-met MH - RNA, Messenger/analysis MH - Rats MH - Receptor Protein-Tyrosine Kinases/*analysis/genetics MH - Tumor Cells, Cultured EDAT- 1994/03/01 00:00 MHDA- 1994/03/01 00:01 CRDT- 1994/03/01 00:00 PHST- 1994/03/01 00:00 [pubmed] PHST- 1994/03/01 00:01 [medline] PHST- 1994/03/01 00:00 [entrez] AID - 10.1007/BF01753981 [doi] PST - ppublish SO - Clin Exp Metastasis. 1994 Mar;12(2):143-54. doi: 10.1007/BF01753981.