Oncotarget

Research Papers:

Increased expression of deleted in malignant brain tumors (DMBT1) gene in precancerous gastric lesions: Findings from human and animal studies

Jone Garay _, M. Blanca Piazuelo, Lizbeth Lopez-Carrillo, Yelda A. Leal, Sumana Majumdar, Li Li, Nataly Cruz-Rodriguez, Silvia J. Serrano-Gomez, Carlos S. Busso, Barbara G. Schneider, Alberto G. Delgado, Luis E. Bravo, Angela M. Crist, Stryder M. Meadows, M. Constanza Camargo, Keith T. Wilson, Pelayo Correa and Jovanny Zabaleta

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Oncotarget. 2017; 8:47076-47089. https://doi.org/10.18632/oncotarget.16792

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Abstract

Jone Garay1, M. Blanca Piazuelo2, Lizbeth Lopez-Carrillo3, Yelda A. Leal4, Sumana Majumdar1, Li Li1, Nataly Cruz-Rodriguez1,5,6, Silvia J. Serrano-Gomez1,5,6, Carlos S. Busso7, Barbara G. Schneider2, Alberto G. Delgado2, Luis E. Bravo8, Angela M. Crist9, Stryder M. Meadows9, M. Constanza Camargo10, Keith T. Wilson2,11, Pelayo Correa2 and Jovanny Zabaleta1,12

1Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA

2Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

3Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico

4Unidad de Investigación Médica Yucatán de la Unidad Médica de Alta Especialidad (UMAE) del Instituto Mexicano del Seguro Social (IMSS), Yucatán, Mexico

5Pontificia Universidad Javeriana, Bogotá, Colombia

6Grupo de Investigacion en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá, Colombia

7Department of Otorhinolaryngology, LSUHSC, New Orleans, LA, USA

8Department of Pathology, Universidad del Valle, Cali, Colombia

9Department of Cell and Molecular Biology Tulane University, New Orleans LA, USA

10Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

11Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA

12Department of Pediatrics, LSUHSC, New Orleans, LA, USA

Correspondence to:

Jovanny Zabaleta, email: jzabal@lsuhsc.edu

Keywords: precancerous gastric lesions, DMBT1, H. pylori, inflammation, gastric cancer

Received: October 25, 2016    Accepted: March 16, 2017    Published: April 03, 2017

ABSTRACT

Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Initial studies showed its deletion and loss of expression in a variety of tumors but the role of this gene in tumor development is not completely understood. Here, we examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African American and Hispanic individuals as well as in the development of gastric pathology in a mouse model of H. pylori infection. We found that in 3 different populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in individuals with dysplasia compared to multifocal atrophic gastritis without intestinal metaplasia; the increase was also observed in individuals with advanced gastritis and positive H. pylori infection. In our animal model, H. pylori infection of Dmbt1-/- mice resulted in significantly higher levels of gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the animal model suggest that in response to H. pylori infection DMBT1 may mediate mucosal protection reducing the risk of developing gastric precancerous lesions. However, the increased expression in human gastric precancerous lesions points to a more complex role of DMBT1 in gastric carcinogenesis.


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