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Evil invaders - Cancer stem cells needed for metastatic growth

Munich, 09/17/2007

Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Stem cells have been implicated in pancreatic tumor growth, but the specific role of these cancer stem cells in tumor biology, including metastasis, is still unclear. In collaboration, researchers at the Ludwig-Maximilians-Universität (LMU) Munich have found that human pancreatic cancer tissue contains cancer stem cells that are defined by specific proteins on their surface. As reported in the science journal “Cell Stem Cell”, these cells exclusively promote tumor growth while being highly resistant to standard chemotherapy. In the surrounding healthy tissue – the tumor’s invasive front – yet another subpopulation of cancer stem cells with one more distinctive marker on the surface is active. They are solely responsible for metastatic growth. Removal or inhibition of these migratory cells did not affect tumor growth but prevented any metastatic activity. New therapies aiming at the elimination of these cells might, in effect, inhibit metastasis in pancreatic cancer.

Stem cells have the potential to differentiate into all other cell types. This extraordinary ability lets patients and doctors alike hope that these cells will eventually provide a cure for degenerative diseases. But there is another side to stem cells as well: Increasing evidence suggests that genetically mutated variants play a crucial role in cancer development and metastasis. Often they cannot be targeted by standard therapies because they are well protected by cellular defense mechanisms. The Munich research team has isolated tumor stem cells defined by expression of CD133, a stem cell marker, from pancreatic tumors. These cells, when implanted into mice, will exclusively trigger the growth of tumors and metastases.

The team then identified a subset of CD133+ cells, which also expressed the chemokine receptor CXCR4, at the tumor’s interface with healthy tissue. When these cells were injected into mice, they formed both primary tumors and metastases. However, when they were pretreated with neutralizing antibodies to CXCR4 or depleted for these CXCR4+ cells, the cells lost their ability to metastasize while tumorigenicity was still preserved. “We tested tissue samples of human patients suffering from pancreatic cancer,” reports project leader Professor Christopher Heeschen, Department of Surgery at LMU. “We found that tumors with a high percentage of malignant stem cells showed a strong migratory activity. We’re now working on the molecular characterization of these cells as one step further toward the development of new therapeutic approaches.”

Publication:
”Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer”,
Patrick C. Hermann, Stephan L. Huber, Tanja Herrler, Alexandra Aicher, Joachim W. Ellwart, Markus Guba, Christiane J. Bruns, and Christopher Heeschen,
Cell Stem Cell, September 13, 2007
DOI 10.1016/j.stem.2007.06.002

Contact:
Professor Dr. Christopher Heeschen
Experimental Medicine, Department of Surgery at the LMU
Tel.: +49-89-7095-3438
Fax: +49-89-7095-6433
E-Mail: christopher.heeschen@med.uni-muenchen.de