Stimulatory effects of hepatocyte growth factor on normal and
neoplastic human bronchial epithelial cells.
Singh-Kaw, Praveena, Reza Zarnegar, and Jill M. Siegfried.
Department of Biochemistry, State University of New York-Roswell
Park Division, Buffalo, NY 14263; Department of Pathology, University
of Pittsburgh, School of Medicine, Pittsburgh, PA 15261; and
Department of Pharmacology, University of Pittsburgh School of
Medicine, Pittsburgh, PA 15261
APStracts 2:0016L, 1995.
We examined the mitogenic, chemoinvasive and chemotactic effects of
hepatocyte growth factor (HGF) towards normal and neoplastic human
epithelial cells derived from the bronchial mucosa. Primary cultures
of human bronchial epithelial cells (HBE cells), immortalized
bronchial epithelial cells (IB3-1 cells) and cells derived from a
squamous cell carcinoma of the lung (128-88T cells) were used as
targets. HGF was mitogenic for all three cell types as measured by
bromodeoxyuridine labeling (BrdU) and colony forming efficiency
(CFE). By BrdU labeling, 9.8-16.8% of nuclei were labeled in controls
versus 56.9-65.6% labeled nuclei in cells treated with HGF. HGF
stimulated colony formation 3.6- to 6.2-fold over untreated control.
Analysis by reverse transcription-polymerase chain reaction
demonstrated the presence of the c-met gene, the receptor for HGF, in
all three cell types. Cell lysates from all three cell types
contained proteins that were recognized by a c-met antibody as
determined by western blotting. The gene for HGF was not expressed in
any of the cell types, although it was expressed in control MRC5
fibroblasts. No HGF protein could be detected by western blotting in
the conditioned medium from epithelial cells, although it was readily
detectable in medium conditioned by lung fibroblasts. HGF proved to
be a powerful chemotactic agent for all three cell types and also
stimulated invasion into Matrigel, an artificial basement membrane.
The results indicate HGF acts mainly as a paracrine growth factor for
cells derived from the human bronchus, and may play a role in the
growth and progression of lung tumors.
Received 30 September 1994; accepted in final form 28 December
1994.
APS Manuscript Number L287-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.