Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line

Sunitha, Iruvanti, Meighen, Deborah L., Hartman, Dan-Paul, Thompson, Erik W., Byers, Stephen W., & Avigan, Mark I. (1994) Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line. Clinical and Experimental Metastasis, 12(2), pp. 143-154.

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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 motogenic 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.

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ID Code: 71914
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):26 Export Date: 6 May 2014 Source: Scopus PubMed ID: 8306528
Additional URLs:
DOI: 10.1007/BF01753981
ISSN: 1573-7276
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 21 May 2014 04:12
Last Modified: 21 May 2014 04:12

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