Focus: Solving the puzzle of metastasis: the evolution of cell migration in neoplasms

BACKGROUND: Metastasis represents one of the most clinically important transitions in neoplastic progression. The evolution of metastasis is a puzzle because a metastatic clone is at a disadvantage in competition for space and resources with non-metastatic clones in the primary tumor. Metastatic clones waste some of their reproductive potential on emigrating cells with little chance of establishing metastases. We suggest that resource heterogeneity within primary tumors selects for cell migration, and that cell emigration is a by-product of that selection.

METHODS AND FINDINGS: We developed an agent-based model to simulate the evolution of neoplastic cell migration. We simulated the essential dynamics of neoangiogenesis and blood vessel occlusion that lead to resource heterogeneity in neoplasms. We observed the probability and speed of cell migration that evolves with changes in parameters that control the degree of spatial and temporal resource heterogeneity. Across a broad range of realistic parameter values, increasing degrees of spatial and temporal heterogeneity select for the evolution of increased cell migration and emigration.

CONCLUSIONS: We showed that variability in resources within a neoplasm (e.g. oxygen and nutrients provided by angiogenesis) is sufficient to select for cells with high motility. These cells are also more likely to emigrate from the tumor, which is the first step in metastasis and the key to the puzzle of metastasis. Thus, we have identified a novel potential solution to the puzzle of metastasis.

Source: Solving the puzzle of metastasis: the evolution of cell migration in neoplasms. Chen Jun, Sprouffske Kathleen, Huang Qihong, Maley Carlo C (cmaley@alum.mit.edu). PLoS One. 2011 Apr 27;6(4):e17933.

Article freely available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017933

La métastase représente l'un des événements les plus cliniquement importants dans la progression néoplasique. Des chercheurs ont développé un modèle multi-agent pour simuler l'évolution de la migration des cellules néoplasiques. Ils montrent que la variabilité des ressources au sein d'une tumeur (par exemple l'oxygène et les nutriments fournis par l'angiogenèse) est suffisante pour sélectionner les cellules à haute motilité. Ces cellules sont également plus susceptibles de quitter la tumeur.

Article (en anglais) disponible gratuitement à l’adresse : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017933