Research Projects

General aim
We investigate the role of cancer-associated alterations of cell surface glycosylation on malignancy and metastasis progression. Metastatic tumor cells “communicate” with the cells in their microenvironment, which consist predominantly of inflammatory cells. We evaluate the significance of cell-cell communication between tumor cells and inflammatory cells within the tumor microenvironment for initiation of metastasis.

Role of cancer associated glycosylation and selectins in metastasis

Change of cell-surface glycosylation is a universal hallmark of tumorigenesis. There is a significant correlation between altered glycosylation and clinical prognosis by carcinoma patients. Enhanced expression of carcinoma-associated glycan structures carrying selectin ligands correlate with metastatic progression. One of a common glycan epitopes found on carcinomas is the terminal tetrasaccharide sialyl Lewisx and sialyl Lewisa, which consistently correlates with tumor progression, metastatic spread, and poor prognosis. Blood born metastasis is caused by spread of tumor cells through circulation. The selectins are well-characterized vascular receptors for certain sLex/a-containing, mucin-type glycoproteins, suggesting their implication in the process of metastasis. In particular, the facilitating role of leukocytes, through L-selectin-mediated interactions, is in the focus of current investigations.

• investigation of the roles of L- and P-selectin for metastasis in selectin-deficient mice

• investigation of structures and functions of tumor cell glycans and their effect on modulation of metastasis in an mouse model of experimental metastasis

• study of the metastatic microenvironment; identification of molecular mechanisms modulating cancer progression

Methodological approaches

• General molecular and cell biological techniques
  
• Fluorescent microscopy, confocal and deconvolution approaches
  
• Genomics and transcriptomics using gene chip methodology
  
• Mouse models of experimental and spontaneous metastasis
  
• Analysis of tumor glycans
  
• Analysis of heparin derivatives as potential inhibitors of metastasis