Sequential changes of the DMBT1 expression and location in normal lung tissue and lung carcinomas

Abstract

Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain, digestive tract, and lung cancer. Recent studies on its expression in lung cancer have led to divergent results and have raised a controversial discussion. Moreover, DMBT1 has been implicated with epithelial protection in the respiratory tract. We thus wondered how a loss of its expression could be related to carcinogenesis in the lung. To address these issues, we investigated the DMBT1 expression and location in the normal lung and lung cancer. By reverse-transcription PCR, a down-regulation of the DMBT1 expression in lung cancer cell lines is commonly detected. Immunohistochemical studies in situ demonstrate that there are also low steady-state levels of DMBT1 in the normal respiratory epithelium. However, an up-regulation takes place in the tumor-flanking epithelium and upon respiratory inflammation. Lung carcinomas show increased DMBT1 expression compared to that of undiseased lung tissue, but decreased DMBT1 levels compared to that of tumor-flanking and inflammatory tissue. A switch from a lumenal secretion to a secretion to the extracellular matrix takes place during lung carcinogenesis. Our data may resolve the controversial discussion on its expression in lung carcinomas. We hypothesize that the changes of the DMBT1 expression and location do reflect a time course that may point to possible mechanisms for its role in epithelial cancer.

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

“…Indeed, deregulation of DMBT1 expression has been reported for a number of tumors, including gliomas (Lin et al, 1998), small-and non-small-cell lung cancer cell lines and tumors (Takeshita et al, 1999;Wu et al, 1999;Mollenhauer et al, 2002), carcinoma of the esophagus (Mori et al, 1999;Mollenhauer et al, 2001), epithelial skin cancer , intrahepatic cholangiocarcinoma (Sasaki et al, 2003), breast cancer (Braidotti et al, 2004;Mollenhauer et al, 2004;Blackburn et al, 2007), salivary gland tumors (Bikker et al, 2004b), pancreatic ductal adenocarcinomas (Hustinx et al, 2004;Cheung et al, 2008), oral squamous cell carcinoma (Imai et al, 2005), gastric cancer (Conde et al, 2007), and cutaneous melanoma . In many cases, expression of DMBT1/gp340/SAG was deregulated not only at the tumor site but also in flanking tissue, which could arise as a consequence of the proinflammatory environment generated by the tumor.…”

Inactivating mutations of CASPASE-7 gene in human cancers

“…Several candidate tumor-suppressor genes of this region have been identified (Mollenhauer et al, 2001). For example, deleted in malignant brain tumors 1 (DMBT1) gene in this locus has been proposed as a candidate tumorsuppressor gene for brain, lung and digestive tract cancer (Mollenhauer et al, 2001).…”

Regulation of DMBT1 via NOD2 and TLR4 in Intestinal Epithelial Cells Modulates Bacterial Recognition and Invasion

“…2, 4, and 6). An up-regulation of DMBT1 was detected in pulmonary epithelial cells upon inflammatory stimuli in vitro and in vivo (8,9). DMBT1 gp340 interacts with the defense collectins surfactant protein A and surfactant protein D and stimulates migration of alveolar macrophages, suggesting a role for DMBT1 in the cross-talk between epithelial cells and the underlying mucosal immune cells (10).…”