Growth inhibition of human lung adenocarcinoma cells by antibodies against epidermal growth factor receptor and by ganglioside GM3: involvement of receptor-directed protein tyrosine phosphatase(s).
Growth of the EGF receptor-expressing non-small-cell lung carcinoma cell line H125 seems to be at least partially driven by autocrine activation of the resident EGF receptors. Thus, the possibility of an EGF receptor-directed antiproliferative treatment was investigated in vitro using a monoclonal antibody (alpha EGFR ior egf/r3) against the human EGF receptor and gangliosides which are known to possess antiproliferative and anti-tyrosine kinase activity. The moderate growth-inhibitory effect of alpha EGFR ior egf/r3 was strongly potentiated by the addition of monosialoganglioside GM3. Likewise, the combination of alpha EGFR ior egf/r3 and GM3 inhibited EGF receptor autophosphorylation activity in H125 cells more strongly than either agent alone. A synergistic inhibition of EGF receptor autophosphorylation by alpha EGFR ior egf/r3 and GM3 was also observed in the human epidermoid carcinoma cell line A431. In both cell lines, the inhibition of EGF receptor autophosphorylation by GM3 was prevented by pretreatment of the cells with pervanadate, a potent inhibitor of protein tyrosine phosphatases (PTPases). Also, GM3 accelerated EGF receptor dephosphorylation in isolated A431 cell membranes. These findings indicate that GM3 has the capacity to activate EGF receptor-directed PTPase activity and suggest a novel possible mechanism for the regulation of cellular PTPases.
Suarez Pestana
E
E
Centro de Inmunologia Molecular, Havana, Cuba.
Greiser
U
U
Sánchez
B
B
Fernández
L E
LE
Lage
A
A
Perez
R
R
Böhmer
F D
FD
D000230:Adenocarcinoma / Q000473:pathology*; D001597:Benzylidene Compounds / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D005679:G(M3) Ganglioside / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011799:Quinazolines; D011869:Radioligand Assay; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D020032:Tyrphostins
D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D005679:G(M3) Ganglioside; D009570:Nitriles; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases