Comparative in vivo antiangiogenic effects of calreticulin from Trypanosoma cruzi and Homo sapiens sapiens

Victor Toledo,Galia Ramírez,Nandy López,Lorena Aguilar,David Lemus,Carolina H Ribeiro,Carolina Valck,Arturo Ferreira,Ismael Maldonado

doi:10.4067/s0716-97602010000300004

Abstract

Angiogenesis is a complex multi-step process of neovascularization arising from preexisting blood vessels whose generation is regulated by pro- and anti-angiogenic factors. Both Trypanosoma cruzi calreticulin (TcCRT) and its human counterpart (HuCRT) are antiangiogenic. This is the first report where the TcCRT and HuCRT anti-angiogenic properties are compared in vivo. In the chick embryonic chorioallantoid membrane assay (CAM) and at equimolar concentrations, TcCRT displayed significantly higher antiangiogenic activities than its human counterpart. LPS had marginal effects at the concentrations present in the recombinant protein preparations and the TcCRT antiangiogenic effects were largely inhibited by specific polyclonal antibodies, thus, reinforcing the fact that the observed TcCRT effects can be attributed to the parasite-derived molecule and not to the endotoxin. The antiangiogenic TcCRT effects correlate with its anti-tumor in vivo effects, as recently shown in our laboratory.

Highlights

Angiogenesis is a complex multi-step process of neovascularization arising from preexisting blood vessels whose generation is regulated by pro- and anti-angiogenic factors
T. cruzi calreticulin gene (TcCRT), is an immunogenic 45 kDa protein, with more than 50% identity (80% in some functional domains) with the human counterpart (HuCRT)
There has been speculation for decades on the possible mechanisms involved in the in vivo effects that infection with several T. cruzi strains may have on a variety of transplanted and spontaneous tumors in animals and humans (Galliard et al, 1950; Oliveira et al, 2001; Roskin, 1946)

Summary

Introduction

Angiogenesis is a complex multi-step process of neovascularization arising from preexisting blood vessels whose generation is regulated by pro- and anti-angiogenic factors. TcCRT and HuCRT are functionally homologous, including negative regulation of the human complement system (Ferreira et al, 2004; Valck et al, 2010) As a consequence, they promote parasite infectivity (Ramirez et al, 2010).

Results

Conclusion