Y. Xie et al., THE RESISTANCE OF MACROPHAGE-LIKE TUMOR-CELL LINES TO GROWTH-INHIBITION BY LIPOPOLYSACCHARIDE AND PERTUSSIS TOXIN, British Journal of Haematology, 84(3), 1993, pp. 392-401
The process of tumorigenesis is frequently associated with resistance
to growth inhibition by physiological regulators of normal cells. Muri
ne macrophage-like cell lines BAC1.2F5, RAW264, J774.1A and PU5/1.8 we
re resistant to growth inhibition by bacterial lipopolysaccharide (LPS
) and pertussis toxin, agents that blocked growth of primary bone marr
ow-derived macrophages (BMDM) in the presence of macrophage colony-sti
mulating factor (CSF-1). The resistance of the CSF-1-dependent cell li
ne BAC1.2F5 to growth inhibition by pertussis toxin argues against the
possibility that pertussis toxin-sensitive G proteins are essential f
or the pathway of growth stimulation by CSF-1. Conversely, these data
add further weight to the argument that LPS mediates some of its biolo
gical activities by mimicking the action of pertussis toxin and inhibi
ting G protein function. The resistance of cell lines to LPS and pertu
ssis toxin was not correlated with any alteration in the expression of
mRNA encoding any of three pertussis-toxin sensitive G protein alpha
subunits. The pattern of G protein expression was consistent between p
rimary cells and tumour cells, suggesting that this is a differentiati
on marker. In particular, G(i)alpha2 mRNA was expressed at remarkably
high levels in all of the cells. The specificity of LPS resistance was
investigated by studying down-regulation of CSF-I binding and inducti
on of proto-oncogene c-fos and tumour necrosis factor (TNF) mRNA. BAC1
.2F5 cells were LPS-resistant in each of these assays. In CSF-1 bindin
g, RAW2 64 and J774.1A responded in the same way as bone marrow-derive
d macrophages but required higher doses of LPS, whereas c-fos and TNF
mRNA were induced in these cells at concentrations that did not inhibi
t growth. In PU5/1.8 cells, CSF-I binding was already very low and was
not further down-regulated, but c-fos and TNF mRNA was inducible by L
PS. By contrast to primary macrophages. the cell lines did not respond
to LPS with down-regulation of c-fms mRNA, which encodes the CSF-I re
ceptor. Hence, the resistance of macrophage-like tumour cells to LPS a
nd pertussis toxin was specific to the pathways controlling growth, an
d was correlated with altered regulation of the CSF-1 receptor.