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Expression of colony-stimulating factor genes by normal human mesothelial
cells and human malignant mesothelioma cells lines in vitro
GD Demetri, BW Zenzie, JG Rheinwald and JD Griffin
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
We investigated normal human mesothelial cells and human malignant
mesothelioma cell lines for the ability to produce hematopoietic colony-
stimulating factors (CSFs) in culture. Early passage cultures of normal
diploid human mesothelial cells spontaneously expressed detectable levels
of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or
G-CSF. Exposure of normal mesothelial cells to epidermal growth factor
(EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced
expression of G-CSF mRNA. The combination of EGF and TNF induced threefold
more G-CSF transcripts than did either factor alone. GM-CSF transcripts
were induced only by the combination of TNF and EGF. Interleukin-1 beta
(IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited
by hydrocortisone (HC). All malignant mesothelioma cell lines tested also
spontaneously expressed M-CSF transcripts. However, in contrast to normal
mesothelial cells, two of four malignant mesothelioma cell lines also
autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or
LPS stimulation. Secretion of biologically active CSFs was confirmed by
testing media conditioned by the various cell types examined. The detection
of biologically active CSFs correlated well with the presence of detectable
CSF transcripts by Northern analysis. These data indicate that (a) normal
human mesothelial cells spontaneously express detectable levels of M-CSF
mRNA in culture; (b) EGF is an essential cofactor for optimal induction of
G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to
inflammatory mediators such as LPS and TNF increases the levels of
transcripts for CSFs and IL-1 beta; and (d) as compared with normal human
mesothelial cells, some cell lines of human malignant mesothelioma exhibit
aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF,
IL-1 beta, and IL-6.
Volume 74,
Issue 3,
pp. 940-946,
08/15/1989
Copyright © 1989 by The American Society of Hematology
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