[Frontiers in Bioscience E2, 602-613, January 1, 2010]

Cancer stem cells as new therapeutic target to prevent tumour progression and metastasis

Maria-Theresa Mueller, Patrick C. Hermann, Christopher Heeschen

Clinical Research Programme, Stem Cells and Cancer Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Resistance of cancer stem cells to damaging agents
4. The search for similarities and differences between stem cells and cancer stem cells
4.1. Signalling pathways determining stemness
5. Migrating cancer stem cells and epithelial-mesenchymal transition (EMT)
6. The tumour microenvironment
7. Implications for anti-metastatic therapy
8. Current and future challenges for the cancer stem cell model
9. Conclusion
10. References

1. ABSTRACT

Over the past decade, increasing evidence suggested that stem cells play a crucial role not only in the generation of complex multicellular organisms, but also in the development and progression of malignant diseases. For the most abundant tumours, it has been shown that they contain a subset of distinct cancer cells that is exclusively responsible for tumour initiation and propagation These cells are termed cancer stem cells or tumour-initiating cells and they are also highly resistant to chemotherapeutic agents. Because CSC are preferentially endowed with the self-renewal capacity, it has further been hypothesized that they are also exclusively responsible for metastasis. Indeed, we were able to show that pancreatic caner stem cells contain a subpopulation of migrating cancer stem cells characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumour and metastasizing. Laboratories around the world are now aiming to further characterize these cells to eventually identify novel treatment modalities to fight cancer. Thus, cancer stem cells are promising new targets to counteract the growth-promoting and metastatic potential of solid tumours.