Antiangiogenic and antitumor effects of Trypanosoma cruzi Calreticulin.

PLoS Neglected Tropical Diseases
Nandy C LópezArturo Ferreira

Abstract

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. 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...Continue Reading

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Citations

Sep 12, 2013·TheScientificWorldJournal·Edgardo BerrielEduardo Osinaga
Oct 20, 2011·The Journal of Parasitology·Ayoola Oladiran, Miodrag Belosevic
Dec 3, 2014·Microvascular Research·Francisca Hildemagna Guedes-da-SilvaAndre Talvani
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Feb 4, 2011·Trends in Parasitology·Galia RamírezArturo Ferreira

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Methods Mentioned

BETA
flow cytometry
PCR
confocal microscopy

Software Mentioned

GraphPad Prism
Image ProPlus
Adobe Photoshop
LSM510

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