Contact Disorder Makes Cancer Cells Mobile
The loss of the protein VMP1 in cancer cells increases their tendency to detach from the initial tumor - the first step towards metastasis. The reason for this, as scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have shown, is that a loss of VMP1 causes cells to lose their capacity to establish contacts with their neighbors.
What causes tumor cells to leave the tissue and start traveling through the body via lymph or blood? As a rule, it is this change of behavior that turns cancer into a deathly disease, because it is a first seed of dangerous secondary tumors (metastases). Scientists of Professor Annemarie Poustka’s division at the DKFZ, collaborating with colleagues in Göttingen and Graz, have shown that a disruption of contact formation between neighboring cells is among the causes why tumor cells become mobile.
In renal cell cancer the researchers discovered that the gene coding for VMP1 is read significantly less in metastases of the tumor than in cells of the primary tumor. Subsequently, the VMP1 gene activities of various breast cancer cell lines were examined. The investigators found that the VMP1 gene is read less in cells with "invasive potential", which may invade other tissues, than in cells without a tendency to migrate or in cells from healthy breast tissue.
The VMP1 protein, as was shown by special dying, is responsible at the cell surface for the formation of specific contact sites between neighboring cells. When the researchers switched off the production of VMP1 in living cells, these rounded up and stopped forming their typical contacts among each other, which normally hold the tissue together. The results obtained by the Heidelberg researchers suggest that VMP1 is responsible for establishing the initial contact, but it is not permanently inserted at the site of physical contact between neighboring cells.
If VMP1 is experimentally switched off in non-invasive renal cancer cells, the cells develop a tendency to migrate. Thus, in a test that simulates the invasion of tissues in the culture dish, VMP1-negative cells showed a significantly more invasive behavior.
"Whether VMP1 production is actively switched off by the tumor or lost by mutations is something we do not know yet," explains Annemarie Poustka. "We are now investigating whether the VMP1 content of tumor cells may be used as a reliable marker for metastasis."
M. Sauermann, Ö. Sahin, H. Sültmann, F. Hahne, S. Blaszkiewicz, M. Majety, K. Zatloukal, L. Füzesi, A. Poustka, S. Wiemann and D. Arlt: Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. Oncogene 2007, epub ahead of print, DOI: 10.1038/sj.onc.1210743
This research has been performed within the framework of the National Genome Research Network (Nationales Genomforschungsnetz, NGFN), a biomedical research program funded by the German Ministry of Education and Research (BMBF).
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
