Transient injury-dependent up-regulation of CD105 and its specific targeting with an anti-vascular anti-mouse endoglin-nigrin b immunotoxin.
Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-β) superfamily members, is over-expressed in tumor neovasculature and can be targeted with anti-endoglin antibodies, thus becoming an important tool for anti-tumoral therapy. Injury of the mouse tail induced the transient expression of endoglin, this peaking at three days after injury and disappearing six days later. An immunotoxin containing the anti-mouse endoglin rat monoclonal antibody MJ7/18 and the non-toxic ribosome-inactivating protein nigrin b (Ngb) was found to be very active in targeting mouse endoglin in the L929 fibroblast cell line (IC(50) of 4 x 10(-11) M). At that concentration, the immunotoxin lacked unspecific activity. Upon induction of endoglin after injury, the MJ7-Ngb immunotoxin strongly attacked and deranged the injured tail, inducing tissue damage. Such effects were dependent on the age of the animals and were evident in six-week-old mice, but not in eight-month-old mice. Our results indicate that endoglin is up-regulated in newly formed vessels upon injury and can be targeted by the MJ7-Ngb immunotoxin; thus, it could be a useful tool for tumor ablation research.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Valladolid, 47005 Valladolid, Spain.
Raquel
R
Muñoz
Yolanda
Y
Arias
José Miguel
JM
Ferreras
Pilar
P
Jiménez
Maria Ángeles
MÁ
Rojo
Carmelo
C
Bernabéu
Damián
D
Córdoba-Díaz
Tomás
T
Girbés
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D002460:Cell Line; D000071063:Endoglin; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D000922:Immunotoxins / Q000276:immunology / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D010940:Plant Proteins / Q000276:immunology*; D011817:Rabbits; D054788:Ribosome Inactivating Proteins / Q000276:immunology*; D013623:Tail / Q000098:blood supply* / Q000293:injuries*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000071063:Endoglin; C502004:Eng protein, mouse; D000922:Immunotoxins; D047908:Intracellular Signaling Peptides and Proteins; D010940:Plant Proteins; C579416:nigrin b protein, Sambucus nigra; D054788:Ribosome Inactivating Proteins