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Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo
Published on: September 30, 2017
An in vivo role for Trypanosoma cruzi calreticulin in antiangiogenesis
María C Molina1, Viviana Ferreira, Carolina Valck
1Programa Disciplinario de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia, 1027 Santiago, Chile.
Abstract:
Angiogenesis leads to neovascularization from existing blood vessels. It is associated with tumor growth and metastasis and is regulated by pro- and antiangiogenic molecules, some of them currently under clinical trials for cancer treatment. During the last few years we have cloned, sequenced and expressed a Trypanosoma cruzi calreticulin gene (TcCRT). Its product, TcCRT, a 45 kDa protein, is more than 50% identical to human CRT (HuCRT). TcCRT, present on the surface of trypomastigotes, binds both C1q and mannan binding lectin and inhibits the classical activation pathway of human complement. Since TcCRT is highly homologous to a functional antiangiogenic fragment from HuCRT (aa 120-180), recombinant (r) and native (n) TcCRT were tested in their antiangiogenic effects, in the chick embryonic chorioallantoid membrane (CAM) assay. Both proteins mediated highly significant antiangiogenic effects in the in vivo CAM assay. This effect was further substantiated in experiments showing that the plasmid construct pSecTag/TcCRT also displayed significant antiangiogenic properties, as compared to the empty vector. Most likely, the fact that antiangiogenic substances act preferentially on growing neoplasic tissues, but not on already established tumors, is due to their effects on emerging blood vessels. The results shown here indicate that TcCRT, like its human counterpart, has antiangiogenic properties. These properties may explain, at least partly, the reported antineoplasic effect of experimental T. cruzi infection.
Insights
Trypanosoma cruzi calreticulin (TcCRT) exhibits significant antiangiogenic properties, similar to human calreticulin. This finding suggests TcCRT may contribute to the anti-cancer effects observed in experimental Trypanosoma cruzi infections.
Area of Science:
- Molecular biology
- Immunology
- Parasitology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
- Calreticulin (CRT) is a protein involved in various cellular functions, including immune response and angiogenesis.
- Trypanosoma cruzi calreticulin (TcCRT) shares high homology with human CRT and has potential antiangiogenic activity.
Purpose of the Study:
- To investigate the antiangiogenic potential of Trypanosoma cruzi calreticulin (TcCRT).
- To compare the antiangiogenic effects of TcCRT with its human counterpart, HuCRT.
- To explore the implications of TcCRT's antiangiogenic properties in the context of cancer treatment.
Main Methods:
- Cloning, sequencing, and expression of the Trypanosoma cruzi calreticulin gene (TcCRT).
- Assessment of antiangiogenic effects using the chick embryonic chorioallantoid membrane (CAM) assay.
- Evaluation of recombinant (r) and native (n) TcCRT, as well as a plasmid construct (pSecTag/TcCRT).
Main Results:
- Both recombinant and native TcCRT demonstrated significant antiangiogenic effects in the in vivo CAM assay.
- The plasmid construct pSecTag/TcCRT also exhibited significant antiangiogenic properties.
- TcCRT's antiangiogenic activity was comparable to that of its human homolog, HuCRT.
Conclusions:
- TcCRT possesses potent antiangiogenic properties, similar to human calreticulin.
- These findings suggest that TcCRT's antiangiogenic activity may contribute to the anti-neoplastic effects of Trypanosoma cruzi infection.
- TcCRT represents a potential therapeutic target for anti-cancer strategies focused on inhibiting angiogenesis.
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