Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans
| Autor: | Bruno Zene Motta, Annuar Jose Chaguri, Vinicius Kannen, Mariângela Ottoboni Brunaldi, Enio Chaves de Oliveira, Sérgio Britto Garcia |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Chagas disease medicine.medical_specialty Pathology lcsh:Arctic medicine. Tropical medicine Colorectal cancer lcsh:RC955-962 Trypanosoma cruzi Myenteric Plexus Megacolon medicine.disease_cause Risk Assessment Gastroenterology BIOMARCADORES Prostate cancer Internal medicine parasitic diseases Biomarkers Tumor Animals Humans Medicine Chagas Disease Myenteric plexus Neurons Denervation business.industry lcsh:Public aspects of medicine Public Health Environmental and Occupational Health Epithelial Cells lcsh:RA1-1270 Hyperplasia medicine.disease Rats Infectious Diseases Colonic Neoplasms business Carcinogenesis Research Article |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003744 (2015) PLoS Neglected Tropical Diseases |
| Popis: | Background Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. Author Summary The myenteric neuronal activity on colon carcinogenesis is a matter of debate. Chagas disease (a trypanosomiasis-related chronic infection) induces megacolon damaging myenteric neurons. Puzzling, tumors have been rarely reported in chagasic megacolon patients. We reveal here hyperplasia-related high-proliferation occurs in chagasic megacolon, although the risk for colon cancer is reduced. Having carcinogen-exposed rats infected with Trypanosoma cruzi reduced the numbers of myenteric neurons and colon preneoplastic lesions. An experimental model for chemical myenteric denervation was applied in carcinogen-exposed rats revealing that myenteric neurons promote the development of colon preneoplastic lesions. Yet, activity of the fecal content had to be secluded from the myenteric neuronal activity on colon carcinogenesis. Hartmann’s surgical procedure enabled that. This was applied together with carcinogenic exposure and myenteric neuronal denervation ensuring that the neuronal activity is associated with enhanced development of colon carcinogenesis. Taken together, we believe colon tumors are not found within the chagasic megacolon region because the myenteric neuronal density is impaired. These observations shed lights on novel potential cell to cell interactions promoting the colon cancer development. |
| Databáze: | OpenAIRE |
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