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.

CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report that purified CRP-ductin binds human SP-D in a calcium-dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp-340 binding of SP-D. CRP-ductin also showed calcium-dependent binding to both gram-positive and -negative bacteria. A polyclonal antibody raised against gp-340 reacted specifically with CRP-ductin in Western blots. Immunoreactivity to CRP-ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP-ductin and SP-D expression by reverse transcription-PCR. The pancreas was the main site of synthesis of CRP-ductin, but transcripts were also readily amplified from salivary gland, the gastrointestinal tract, liver, testis, uterus and lung. Lung was the main site of synthesis of SP-D, but transcripts were also amplified from uterus, salivary gland, thymus, thyroid gland, pancreas and testis. We conclude that CRP-ductin is the mouse homologue of human gp-340 and that its capacity to bind SP-D as well as gramnegative and gram-positive bacteria suggests a role in mucosal immune defense.

No abstract