THE MHC CLASS-II AND CD44 MOLECULES ARE INVOLVED IN THE INDUCTION OF TUMOR-NECROSIS-FACTOR (TNF) GENE-EXPRESSION BY HUMAN MONOCYTES STIMULATED WITH TUMOR-CELLS
M. Zembala et al., THE MHC CLASS-II AND CD44 MOLECULES ARE INVOLVED IN THE INDUCTION OF TUMOR-NECROSIS-FACTOR (TNF) GENE-EXPRESSION BY HUMAN MONOCYTES STIMULATED WITH TUMOR-CELLS, International journal of cancer, 56(2), 1994, pp. 269-274
Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage
infiltrate surrounding the tumour, but the cellular/molecular interact
ions leading to TNF gene expression in macrophages are unknown. The in
vitro system in which human blood monocytes are stimulated with human
cancer cells for TNF release was used to study such interactions. Mon
oclonal antibodies (MAbs) against various adhesion molecules (LFA-I, L
FA-3, ICAM-1, VNR, VLAbetaI chain) were unable to block TNF production
in co-culture of monocytes with a human pancreatic carcinoma (HPC) ce
ll line. However, anti-CD44 and anti-HLA-DR MAbs effectively blocked T
NF release and TNF-mRNA induction in monocytes. Pre-incubation of mono
cytes with anti-HLA-DR and tumour cells with anti-CD44 MAbs had a simi
lar effect. It was concluded that CD44 molecules are involved in tumou
r-monocyte interactions and that HLA-DR determinants of monocytes are
engaged in signal transduction for TNF gene activation. These findings
may suggest that certain surface determinants of tumour cells act as
ligands for MHC class-II molecules and induce TNF production in monocy
tes. (C) 1994 Wiley-Liss, Inc.