Suppression of tumor growth in vivo by local and systemic 90K level increase.
Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.
Jallal
B
B
Sugen, Inc., Redwood City, California 94063, USA.
Powell
J
J
Zachwieja
J
J
Brakebusch
C
C
Germain
L
L
Jacobs
J
J
Iacobelli
S
S
Ullrich
A
A
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006023:Glycoproteins; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008074:Lipoproteins / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1; D016326:Extracellular Matrix Proteins
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D008074:Lipoproteins; D009363:Neoplasm Proteins; D019010:Vascular Cell Adhesion Molecule-1; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins