Dark Aberrant Crypt Foci with activated Wnt pathway are related to tumorigenesis in the colon of AOM-treated rat

Lu Qing, Jiang Bo, Lin Chen, Shan, Shan Tao

Description

To evaluate the relationship between Aberrant Crypt Foci (ACF) and tumorigenesis, we observed the sequential development from ACF to tumor in the colon of azoxymethane-exposed wistar rats. Methods Sixty wistar rats were sacrificed at different time points after exposure to azoxymethane and the colons were stained with methylene blue for stereomicroscopic analysis. Results We found two types of early lesions: classic ACF and dark ACF. Dark ACF were characterized by dark blue staining, mildly enlarged or small compressed crypts that are not elevated from the surrounding epithelium. Large dark ACF and nascent tumors displayed the same surface morphology. Furthermore, dark ACF grew significantly faster than classic ACF and showed dysplasia without hyperplasia. In contrast, classic ACF showed hyperplasia without dysplasia. Dark ACF has significant higher expression rate of β-catenin (100%) and MMP-7 (81.82%) compared with the expression of β-catenin and MMP-7 in classic ACF (4.84% and 7.87%, respectively). Conclusion Our data indicated that dark ACF is closely related to tumorigenesis while classic ACF is not. Furthermore, Wnt signal pathway was activated during the early period of dark ACF.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2008
• Nombre de lectures: 3
• Langue: English

Extrait

Journal of Experimental & Clinical Cancer Research

BioMedCentral

Open Access Research Dark Aberrant Crypt Foci with activated Wnt pathway are related to tumorigenesis in the colon of AOM-treated rat 1,2 11 1 Qing Lu, Bo Jiang*, Chen Linand Tao Shan

1 2 Address: TheInstitute for Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China andDepartment of Gastroenterology, Guilin Medical College affiliated hospital, Guilin 541001, PR China Email: Qing Lu  [e-mail]; Bo Jiang*  [e-mail]; Chen Lin  [e-mail]; Tao Shan  [e-mail] * Corresponding author

Published: 5 August 2008Received: 31 May 2008 Accepted: 5 August 2008 Journal of Experimental & Clinical Cancer Research2008,27:26 doi:10.1186/1756-9966-27-26 This article is available from: http://www.jeccr.com/content/27/1/26 © 2008 Lu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:To evaluate the relationship between Aberrant Crypt Foci (ACF) and tumorigenesis, we observed the sequential development from ACF to tumor in the colon of azoxymethane-exposed wistar rats. Methods:Sixty wistar rats were sacrificed at different time points after exposure to azoxymethane and the colons were stained with methylene blue for stereomicroscopic analysis. Results:We found two types of early lesions: classic ACF and dark ACF. Dark ACF were characterized by dark blue staining, mildly enlarged or small compressed crypts that are not elevated from the surrounding epithelium. Large dark ACF and nascent tumors displayed the same surface morphology. Furthermore, dark ACF grew significantly faster than classic ACF and showed dysplasia without hyperplasia. In contrast, classic ACF showed hyperplasia without dysplasia. Dark ACF has significant higher expression rate ofβ-catenin (100%) and MMP-7 (81.82%) compared with the expression ofβ-catenin and MMP-7 in classic ACF (4.84% and 7.87%, respectively). Conclusion:Our data indicated that dark ACF is closely related to tumorigenesis while classic ACF is not. Furthermore, Wnt signal pathway was activated during the early period of dark ACF.

Background Aberrant crypt foci (ACF) were first described by Bird and Good. The lesion of ACF is composed of the enlarged crypts that are slightly elevated above the surrounding mucosa and the densely stained crypts with methylene blue [1]. ACF are considered as putative preneoplastic lesions of the colon in both humans and experimental animals [2,3].

Although ACF may share some morphologic, genetic, and biochemical features with colonic tumors [47], conflict ing evidence has also been reported. For example, muta

tions in the Krasgene are relatively common in human ACF, but are only detected at a relatively late stage of colon cancer [811]. In rat models, although hundreds of ACF are induced per animal by azoxymethane (AOM), and K rasmutations are frequently observed in those ACF, only a few colon tumors are observed per animal [1214]. In azoxymethane/dimethylhydrazinetreated rats and in patients with sporadic colorectal cancer, the number of tumors is minuscule compared with the large number of ACF [15], demonstrating that only a very small fraction of the ACF in theory has the potential to progress to the stage of a tumor. Therefore, there is a strong need to investigate

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