antiangiogenic and antitumor effects of trypanosoma cruzi calreticulin鲁兹锥体calreticulin反血管增生和抗肿瘤效果.pdf

Antiangiogenic and Antitumor Effects of Trypanosoma cruzi Calreticulin ´ 1 1 ´ 1 ´ 1 1 Nandy C. Lopez , Carolina Valck , Galia Ramırez , Margarita Rodrıguez , Carolina Ribeiro , Juana Orellana1, Ismael Maldonado 1, Adriana Albini2, Daniel Anacona 1, David Lemus 1, Lorena Aguilar 1, Wilhelm Schwaeble3, Arturo Ferreira 1* 1 Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile, 2 Oncology Research, Science and Technology Pole, IRCCS Multimedica, Milan, Italy, 3 Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom Abstract 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. Metho