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

// Jone Garay 1 , M. Blanca Piazuelo 2 , Lizbeth Lopez-Carrillo 3 , Yelda A. Leal 4 , Sumana Majumdar 1 , Li Li 1 , Nataly Cruz-Rodriguez 1, 5, 6 , Silvia J. Serrano-Gomez 1, 5, 6 , Carlos S. Busso 7 , Barbara G. Schneider 2 , Alberto G. Delgado 2 , Luis E. Bravo 8 , Angela M. Crist 9 , Stryder M. Meadows 9 , M. Constanza Camargo 10 , Keith T. Wilson 2, 11 , Pelayo Correa 2 and Jovanny Zabaleta 1, 12 1 Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA 2 Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 3 Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico 4 Unidad de Investigacion Medica Yucatan de la Unidad Medica de Alta Especialidad (UMAE) del Instituto Mexicano del Seguro Social (IMSS), Yucatan, Mexico 5 Pontificia Universidad Javeriana, Bogota, Colombia 6 Grupo de Investigacion en Biologia del Cancer, Instituto Nacional de Cancerologia, Bogota, Colombia 7 Department of Otorhinolaryngology, LSUHSC, New Orleans, LA, USA 8 Department of Pathology, Universidad del Valle, Cali, Colombia 9 Department of Cell and Molecular Biology Tulane University, New Orleans LA, USA 10 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA 11 Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA 12 Department 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.