Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

Genetic heterogeneity of Trypanosoma cruzi and its direct anticancer effect in cultured human tumor cells

The direct inhibitory effect of Trypanosoma cruzi epimastigote lysates on in vitro cultured human breast cancer MCF-7 cells differs in various genetic groups and cloned subgroups of Trypanosoma

In vivo anticancer activity of lysates from Trypanosoma cruzi of different genetic groups

Lyzed epimastigotes of Trypanosoma cruzi clones P209-1, Gamba1, Sp104-1, MASu, Y7/1, MN12, Cl-Brener, 86/2036, Y7/2-1 inhibit the growth of Ehrlich adenocarcinoma in mice. The tumor decreased 1.5-3 times after 12 daily injections of lysates from 15 million epimastigotes. The protective effect progressed after the injections were discontinued and depended on the dose and lysate producer clone. Trypanosoma lysates in the studied doses were nontoxic. © Springer Science+Business Media, Inc. 2006

The study of immunological component in antitumor effect of Trypanosoma cruzi

The experiments with passive transfer of splenocytes obtained from animals immunized with Trypanosoma cruzi lysate revealed the role of cell-mediated component of the immunity in the antitumor effect of T. cruzi. The common features of T. cruzi antigens and tumor-specific antigens of Ehrlich's adenocarcinoma were demonstrated. These antigens were shown to have common epitopes with mammalian mucins. The oncoprotective effect was achieved by immunization with type II and III mucins and was reproduced after passive transfer of splenocytes from immunized animals. © Springer Science+Business Media, Inc. 2008

In vivo anticancer activity of lysates from Trypanosoma cruzi of different genetic groups

Lyzed epimastigotes of Trypanosoma cruzi clones P209-1, Gamba1, Sp104-1, MASu, Y7/1, MN12, Cl-Brener, 86/2036, Y7/2-1 inhibit the growth of Ehrlich adenocarcinoma in mice. The tumor decreased 1.5-3 times after 12 daily injections of lysates from 15 million epimastigotes. The protective effect progressed after the injections were discontinued and depended on the dose and lysate producer clone. Trypanosoma lysates in the studied doses were nontoxic. © Springer Science+Business Media, Inc. 2006

The study of immunological component in antitumor effect of Trypanosoma cruzi

The experiments with passive transfer of splenocytes obtained from animals immunized with Trypanosoma cruzi lysate revealed the role of cell-mediated component of the immunity in the antitumor effect of T. cruzi. The common features of T. cruzi antigens and tumor-specific antigens of Ehrlich's adenocarcinoma were demonstrated. These antigens were shown to have common epitopes with mammalian mucins. The oncoprotective effect was achieved by immunization with type II and III mucins and was reproduced after passive transfer of splenocytes from immunized animals. © Springer Science+Business Media, Inc. 2008