Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin.
BACKGROUND: In Latin America, 18 million people are infected with Trypanosoma cruzi, the agent of Chagas' disease, with the greatest economic burden. Vertebrate calreticulins (CRT) are multifunctional, intra- and extracellular proteins. In the endoplasmic reticulum (ER) they bind calcium and ac...
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ftdoajarticles:oai:doaj.org/article:43da14bbae7b405a8510a01d434d77b6 2023-05-15T15:16:27+02:00 Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. Nandy C López Carolina Valck Galia Ramírez Margarita Rodríguez Carolina Ribeiro Juana Orellana Ismael Maldonado Adriana Albini Daniel Anacona David Lemus Lorena Aguilar Wilhelm Schwaeble Arturo Ferreira 2010-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000730 https://doaj.org/article/43da14bbae7b405a8510a01d434d77b6 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2897838?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000730 https://doaj.org/article/43da14bbae7b405a8510a01d434d77b6 PLoS Neglected Tropical Diseases, Vol 4, Iss 7, p e730 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000730 2022-12-31T16:02:49Z BACKGROUND: In Latin America, 18 million people are infected with Trypanosoma cruzi, the agent of Chagas' disease, with the greatest economic burden. Vertebrate calreticulins (CRT) are multifunctional, intra- and extracellular proteins. In the endoplasmic reticulum (ER) they bind calcium and act as chaperones. Since human CRT (HuCRT) is antiangiogenic and suppresses tumor growth, the presence of these functions in the parasite orthologue may have consequences in the host/parasite interaction. Previously, we have cloned and expressed T. cruzi calreticulin (TcCRT) and shown that TcCRT, translocated from the ER to the area of trypomastigote flagellum emergence, promotes infectivity, inactivates the complement system and inhibits angiogenesis in the chorioallantoid chicken egg membrane. Most likely, derived from these properties, TcCRT displays in vivo inhibitory effects against an experimental mammary tumor. METHODOLOGY AND PRINCIPAL FINDINGS: TcCRT (or its N-terminal vasostatin-like domain, N-TcCRT) a) Abrogates capillary growth in the ex vivo rat aortic ring assay, b) Inhibits capillary morphogenesis in a human umbilical vein endothelial cell (HUVEC) assay, c) Inhibits migration and proliferation of HUVECs and the human endothelial cell line Eahy926. In these assays TcCRT was more effective, in molar terms, than HuCRT: d) In confocal microscopy, live HUVECs and EAhy926 cells, are recognized by FITC-TcCRT, followed by its internalization and accumulation around the host cell nuclei, a phenomenon that is abrogated by Fucoidin, a specific scavenger receptor ligand and, e) Inhibits in vivo the growth of the murine mammary TA3 MTXR tumor cell line. CONCLUSIONS/SIGNIFICANCE: We describe herein antiangiogenic and antitumor properties of a parasite chaperone molecule, specifically TcCRT. Perhaps, by virtue of its capacity to inhibit angiogenesis (and the complement system), TcCRT is anti-inflammatory, thus impairing the antiparasite immune response. The TcCRT antiangiogenic effect could also explain, at least partially, ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 7 e730 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Nandy C López Carolina Valck Galia Ramírez Margarita Rodríguez Carolina Ribeiro Juana Orellana Ismael Maldonado Adriana Albini Daniel Anacona David Lemus Lorena Aguilar Wilhelm Schwaeble Arturo Ferreira Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: In Latin America, 18 million people are infected with Trypanosoma cruzi, the agent of Chagas' disease, with the greatest economic burden. Vertebrate calreticulins (CRT) are multifunctional, intra- and extracellular proteins. In the endoplasmic reticulum (ER) they bind calcium and act as chaperones. Since human CRT (HuCRT) is antiangiogenic and suppresses tumor growth, the presence of these functions in the parasite orthologue may have consequences in the host/parasite interaction. Previously, we have cloned and expressed T. cruzi calreticulin (TcCRT) and shown that TcCRT, translocated from the ER to the area of trypomastigote flagellum emergence, promotes infectivity, inactivates the complement system and inhibits angiogenesis in the chorioallantoid chicken egg membrane. Most likely, derived from these properties, TcCRT displays in vivo inhibitory effects against an experimental mammary tumor. METHODOLOGY AND PRINCIPAL FINDINGS: TcCRT (or its N-terminal vasostatin-like domain, N-TcCRT) a) Abrogates capillary growth in the ex vivo rat aortic ring assay, b) Inhibits capillary morphogenesis in a human umbilical vein endothelial cell (HUVEC) assay, c) Inhibits migration and proliferation of HUVECs and the human endothelial cell line Eahy926. In these assays TcCRT was more effective, in molar terms, than HuCRT: d) In confocal microscopy, live HUVECs and EAhy926 cells, are recognized by FITC-TcCRT, followed by its internalization and accumulation around the host cell nuclei, a phenomenon that is abrogated by Fucoidin, a specific scavenger receptor ligand and, e) Inhibits in vivo the growth of the murine mammary TA3 MTXR tumor cell line. CONCLUSIONS/SIGNIFICANCE: We describe herein antiangiogenic and antitumor properties of a parasite chaperone molecule, specifically TcCRT. Perhaps, by virtue of its capacity to inhibit angiogenesis (and the complement system), TcCRT is anti-inflammatory, thus impairing the antiparasite immune response. The TcCRT antiangiogenic effect could also explain, at least partially, ... |
format |
Article in Journal/Newspaper |
author |
Nandy C López Carolina Valck Galia Ramírez Margarita Rodríguez Carolina Ribeiro Juana Orellana Ismael Maldonado Adriana Albini Daniel Anacona David Lemus Lorena Aguilar Wilhelm Schwaeble Arturo Ferreira |
author_facet |
Nandy C López Carolina Valck Galia Ramírez Margarita Rodríguez Carolina Ribeiro Juana Orellana Ismael Maldonado Adriana Albini Daniel Anacona David Lemus Lorena Aguilar Wilhelm Schwaeble Arturo Ferreira |
author_sort |
Nandy C López |
title |
Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
title_short |
Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
title_full |
Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
title_fullStr |
Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
title_full_unstemmed |
Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin. |
title_sort |
antiangiogenic and antitumor effects of trypanosoma cruzi calreticulin. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000730 https://doaj.org/article/43da14bbae7b405a8510a01d434d77b6 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 7, p e730 (2010) |
op_relation |
http://europepmc.org/articles/PMC2897838?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000730 https://doaj.org/article/43da14bbae7b405a8510a01d434d77b6 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000730 |
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PLoS Neglected Tropical Diseases |
container_volume |
4 |
container_issue |
7 |
container_start_page |
e730 |
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1766346753492123648 |