Transient Injury-Dependent Up-Regulation of CD105 and its Specific Targeting with an Anti-Vascular Anti-Mouse Endoglin-Nigrin b Immunotoxin

Raquel      Munoz; Yolanda      Arias; Jose      Miguel Ferreras; Pilar      Jimenez; Maria      Angeles Rojo; Carmelo      Bernabeu; Damian      Cordoba-Diaz; Tomas      Girbes

doi:10.2174/1573406411208060996

Abstract

Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-) 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 (IC50 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.

Keywords: Anti-endoglin Antibody, Anti-tumor Therapy, CD105, CD105 Ablation, Endoglin, Nigrin b

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