Expression of invasion-related extracellular matrix molecules in human glioblastoma versus intracerebral lung adenocarcinoma metastasis

Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection, with tumor recurrence in the form of microdisseminated disease. Extracellular matrix (ECM)-related molecules and their receptors predominantly participate in the invasion process, including cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the healthy brain by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 30 invasion-related molecules (twenty-one ECM components, two related receptors, and seven ECM-related enzymes) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM), intracerebral lung adenocarcinoma metastasis, and normal brain were evaluated. Significant differences were established for 24 of the 30 molecules. To confirm our results at the protein level, immunohistochemical analysis of seven molecules was performed (agrin, neurocan, syndecan, versican, matrix metalloproteinase 2 [MMP-2], MMP-9, and hyaluronan). Determining the differences in the levels of invasion-related molecules for tumors of different origins can help to identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas

Differentiation and Glucocorticoid Regulated Apopto-Phagocytic Gene Expression Patterns in Human Macrophages. Role of Mertk in Enhanced Phagocytosis

The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk