Limits...
Is it all That Bad When Living with an Intracellular Protozoan? The Role of Trypanosoma cruzi Calreticulin in Angiogenesis and Tumor Growth.

Ramírez-Toloza G, Aguilar-Guzmán L, Valck C, Abello P, Ferreira A - Front Oncol (2015)

Bottom Line: We have shown that T. cruzi CRT (TcCRT) better executes the antiangiogenic and anti-tumor effects of mammal CRT and its N-terminus vasostatin.In this regard, recombinant TcCRT (rTcCRT) and/or its N-terminus inhibit angiogenesis in vitro, ex vivo, and in vivo.TcCRT also inhibits the growth of murine adenocarcinomas and melanomas.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Medicine and Livestock Sciences, University of Chile , Santiago , Chile.

ABSTRACT
The immune system protects against disease, but may aberrantly silence immunity against "altered self," with consequent development of malignancies. Among the components of the endoplasmic reticulum (ER), important in immunity, is calreticulin (CRT) that, in spite of its residence in the ER, can be translocated to the exterior. Trypanosoma cruzi is the agent of Chagas disease, one of the most important global neglected infections, affecting several hundred thousand people. The syndrome, mainly digestive and circulatory, affects only one-third of those infected. The anti-tumor effects of the infection are known for several decades, but advances in the identification of responsible T. cruzi molecules are scarce. We have shown that T. cruzi CRT (TcCRT) better executes the antiangiogenic and anti-tumor effects of mammal CRT and its N-terminus vasostatin. In this regard, recombinant TcCRT (rTcCRT) and/or its N-terminus inhibit angiogenesis in vitro, ex vivo, and in vivo. TcCRT also inhibits the growth of murine adenocarcinomas and melanomas. Finally, rTcCRT fully reproduces the anti-tumor effect of T. cruzi infection in mice. Thus, we hypothesize that, the long reported anti-tumor effect of T. cruzi infection is mediated at least in part by TcCRT.

No MeSH data available.


Related in: MedlinePlus

Trypanosoma cruzi CRT-mediated tumor growth inhibition. In both experiments, 5 × 105 murine A/J mammary tumor (TA3 MTXR) cells were inoculated s.c. in A/J female mice, five animals per group. (A,B) Together with tumor cells, and every other day, the animals were inoculated s.c. with 50 μg TcCRT or HuCRT or solvent. While TcCRT had a similar anti-tumor effect in both experiments (p = 0.0078), HuCRT did not show that effect under these conditions (13). In both experiments, the tumor size was determined with a digital caliper (Mitutoyo Corp., Japan), in a double blind procedure. The formula (π/6 × length × width2) was used. Data were statistically validated by Wilcoxon Signed Rank test, GraphPad Prism 4. Reproduced with permission from PLoS Neglected Tropical Diseases (13).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4292450&req=5

Figure 1: Trypanosoma cruzi CRT-mediated tumor growth inhibition. In both experiments, 5 × 105 murine A/J mammary tumor (TA3 MTXR) cells were inoculated s.c. in A/J female mice, five animals per group. (A,B) Together with tumor cells, and every other day, the animals were inoculated s.c. with 50 μg TcCRT or HuCRT or solvent. While TcCRT had a similar anti-tumor effect in both experiments (p = 0.0078), HuCRT did not show that effect under these conditions (13). In both experiments, the tumor size was determined with a digital caliper (Mitutoyo Corp., Japan), in a double blind procedure. The formula (π/6 × length × width2) was used. Data were statistically validated by Wilcoxon Signed Rank test, GraphPad Prism 4. Reproduced with permission from PLoS Neglected Tropical Diseases (13).

Mentions: In agreement with the previously described facts, inoculation of rTcCRT inhibits by 60–70% the time-course development of a murine mammary metrotexate multiresistant adenocarcinoma (TA3-MTX-R), with a higher efficiency than the human counterpart (13) (Figure 1).


Is it all That Bad When Living with an Intracellular Protozoan? The Role of Trypanosoma cruzi Calreticulin in Angiogenesis and Tumor Growth.

Ramírez-Toloza G, Aguilar-Guzmán L, Valck C, Abello P, Ferreira A - Front Oncol (2015)

Trypanosoma cruzi CRT-mediated tumor growth inhibition. In both experiments, 5 × 105 murine A/J mammary tumor (TA3 MTXR) cells were inoculated s.c. in A/J female mice, five animals per group. (A,B) Together with tumor cells, and every other day, the animals were inoculated s.c. with 50 μg TcCRT or HuCRT or solvent. While TcCRT had a similar anti-tumor effect in both experiments (p = 0.0078), HuCRT did not show that effect under these conditions (13). In both experiments, the tumor size was determined with a digital caliper (Mitutoyo Corp., Japan), in a double blind procedure. The formula (π/6 × length × width2) was used. Data were statistically validated by Wilcoxon Signed Rank test, GraphPad Prism 4. Reproduced with permission from PLoS Neglected Tropical Diseases (13).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4292450&req=5

Figure 1: Trypanosoma cruzi CRT-mediated tumor growth inhibition. In both experiments, 5 × 105 murine A/J mammary tumor (TA3 MTXR) cells were inoculated s.c. in A/J female mice, five animals per group. (A,B) Together with tumor cells, and every other day, the animals were inoculated s.c. with 50 μg TcCRT or HuCRT or solvent. While TcCRT had a similar anti-tumor effect in both experiments (p = 0.0078), HuCRT did not show that effect under these conditions (13). In both experiments, the tumor size was determined with a digital caliper (Mitutoyo Corp., Japan), in a double blind procedure. The formula (π/6 × length × width2) was used. Data were statistically validated by Wilcoxon Signed Rank test, GraphPad Prism 4. Reproduced with permission from PLoS Neglected Tropical Diseases (13).
Mentions: In agreement with the previously described facts, inoculation of rTcCRT inhibits by 60–70% the time-course development of a murine mammary metrotexate multiresistant adenocarcinoma (TA3-MTX-R), with a higher efficiency than the human counterpart (13) (Figure 1).

Bottom Line: We have shown that T. cruzi CRT (TcCRT) better executes the antiangiogenic and anti-tumor effects of mammal CRT and its N-terminus vasostatin.In this regard, recombinant TcCRT (rTcCRT) and/or its N-terminus inhibit angiogenesis in vitro, ex vivo, and in vivo.TcCRT also inhibits the growth of murine adenocarcinomas and melanomas.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Medicine and Livestock Sciences, University of Chile , Santiago , Chile.

ABSTRACT
The immune system protects against disease, but may aberrantly silence immunity against "altered self," with consequent development of malignancies. Among the components of the endoplasmic reticulum (ER), important in immunity, is calreticulin (CRT) that, in spite of its residence in the ER, can be translocated to the exterior. Trypanosoma cruzi is the agent of Chagas disease, one of the most important global neglected infections, affecting several hundred thousand people. The syndrome, mainly digestive and circulatory, affects only one-third of those infected. The anti-tumor effects of the infection are known for several decades, but advances in the identification of responsible T. cruzi molecules are scarce. We have shown that T. cruzi CRT (TcCRT) better executes the antiangiogenic and anti-tumor effects of mammal CRT and its N-terminus vasostatin. In this regard, recombinant TcCRT (rTcCRT) and/or its N-terminus inhibit angiogenesis in vitro, ex vivo, and in vivo. TcCRT also inhibits the growth of murine adenocarcinomas and melanomas. Finally, rTcCRT fully reproduces the anti-tumor effect of T. cruzi infection in mice. Thus, we hypothesize that, the long reported anti-tumor effect of T. cruzi infection is mediated at least in part by TcCRT.

No MeSH data available.


Related in: MedlinePlus