HER/erbB receptors as therapeutic targets of immunotoxins in human rhabdomyosarcoma cells.
Human rhabdomyosarcoma cells express HER/erbB growth factors receptors. Receptors belonging to this family are overexpressed and play a role in many types of epithelial and neural cancer and have been selected as targets for cancer therapy. In this paper EGF-R, HER-2 and HER-3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma. Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF-R, HER-2 and HER-3 followed by secondary F(ab')2 antimouse immunoglobulin linked to saporin-S6, a type 1 ribosome-inactivating protein (RIP) from the seeds of Saponaria officinalis. The indirect immunotoxin targeting EGF-R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells, whereas indirect immunotoxins against HER-2 and HER-3 were ineffective. The toxic activity of anti-EGF-R immunotoxin was also observed on rhabdomyosarcoma cells expressing low level of EGF-R. EGF-R could be a novel therapeutic target of immunotoxins in human rhabdomyosarcoma.
Ricci
Cinzia
C
Section of Cancer Research, Department of Experimental Pathology, University of Bologna, Italy.
Polito
Letizia
L
Nanni
Patrizia
P
Landuzzi
Lorena
L
Astolfi
Annalisa
A
Nicoletti
Giordano
G
Rossi
Ilaria
I
De Giovanni
Carla
C
Bolognesi
Andrea
A
Lollini
Pier-Luigi
PL
D000911:Antibodies, Monoclonal / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007167:Immunotherapy; D000922:Immunotoxins / Q000276:immunology; D009699:N-Glycosyl Hydrolases / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology; D012208:Rhabdomyosarcoma; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011971:Receptors, Immunologic; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; C052643:F(ab')2 receptor