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Welcome at MCSCs.eu!

MCSCs stands for “migrating cancer stem cells” and is the acronym of our consortium of European scientists supported by the Sixth Framework Programme (FP6) of the European Union (EU). In particular, the main aim of our EU consortium is to study the molecular and cellular mechanisms underlying the onset and behavior of a subset of tumor cells, often referred to as cancer stem cells (CSCs), known to play rate-limiting roles in colon and breast cancer formation and metastasis. This web site is meant to inform both the general public and cancer professionals about this novel and revolutionary concept in cancer research, and the progress made by our EU consortium and the scientific community at large to elucidate the mechanisms governing their onset and malignant behavior and the development of ‘tailor-made’ therapeutic strategies targeted at CSCs.

 

 

 

Cancer is generally thought to arise from normal tissues along a multi-step progression from precursor lesions to increasingly more invasive (malignant) stages. Local and distant metastases arise from these primary malignant lesions and still represent one of the major causes of morbidity and mortality among cancer patients throughout the industrialized world. Along this sequence of events, a stepwise accumulation of genetic alterations in specific cancer genes is considered the driving force in tumor initiation, progression and metastasis. A well-defined number of cellular changes, such as self-sufficiency in growth signals, resistance to programmed cell death (apoptosis), insensitivity to growth-inhibitory signals, limitless replicative potential, and the capacity for inducing growth of new blood vessels (angiogenesis), are thought to represent essential requirements for the cancer cell to grow and invade distant sites.

However, although formally correct, this model takes little account of other essential characteristics of human cancers, namely their pronounced cellular heterogeneity (many different cell types are often present within the tumor mass) and the putative role played by a subpopulation of cells, the cancer stem cells (CSCs), in driving tumor growth and determining local invasion into surrounding tissues and distant metastasis.

Tumors are not autonomously-acting proliferation machines, but are very heterogeneous, both in their morphological and functional aspects. In fact, an individual tumor may show distinct areas of proliferation, cell cycle arrest, epithelial differentiation, cell adhesion and dissemination.
According to this more dynamic CSC model (see figure), the majority of tumor types arise from within stem cell niches characterized by a tightly coordinated balance between self-renewal, migration, proliferation, differentiation and apoptosis. Mutations in genes known to be responsible for this balance in normal tissues result in the formation of a partially differentiatedand heterogeneous tumor mass that, upon additional mutations and under the positive influence of micro-environmental factors, progresses towards malignancy.

Tumor cells are shed from this heterogeneous mass into the micro-environment. However, they will reflect the heterogeneity of the primary tumor and only few, the migrating cancer stem cells, will retain the necessary plasticity to undergo trans-differentiation and enable their migration and homing in distal organs. Accordingly, aggressive cancer progression has been correlated with the loss of epithelial identity and the acquisition of a migratory phenotype. This phenomenon, referred to as epithelial to mesenchymal transition (EMT), is considered a crucial event in malignancy. Additional steps enabling dissemination and metastasis may be reversible (mesenchymal to epithelial transition, MET), and thus cannot solely be explained by irreversible genetic alterations, indicating the existence of a dynamic component to human tumor progression and of a regulatory role for the tumor environment.

Last Updated ( Monday, 01 December 2008 )
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Migrating cancer stem cells (MCSCs) in breast and colon cancer is a Specific Targeted Research or Innivation Project subsidized by the 6th Framework Programme of the European Union, call LSH-2005-2.2.0-5: Exploring the patientís cancer stem cell as a novel therapeutic target, contract no. 037297.
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