'Go or Grow': the key to the emergence of invasion in tumour progression?

• Published in: Mathematical medicine and biology 2012-03, Vol.29 (1), p.49-65
• Main Authors: Hatzikirou, H., Basanta, D., Simon, M., Schaller, K., Deutsch, A.
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - pathology; Brain Neoplasms - physiopathology; Cell Movement; Cell Proliferation; Computer Simulation; Glioblastoma - pathology; Glioblastoma - physiopathology; Humans; Hypoxia - pathology; Hypoxia - physiopathology; Mathematical Concepts; Models, Biological; Mutation; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Invasiveness - physiopathology; Phenotype; Tumor Microenvironment
• ISSN: 1477-8599; 1477-8602
• DOI: 10.1093/imammb/dqq011

Uncontrolled proliferation and abnormal cell migration are two of the main characteristics of tumour growth. Of ultimate importance is the question what are the mechanisms that trigger the progression from benign neoplasms (uncontrolled/autonomous proliferation) to malignant invasive tumours (high migration). In the following, we challenge the currently prevailing view that the emergence of invasiveness is mainly the consequence of acquired cancer cell mutations. To study this, we mainly focus on the 'glioblastoma multiforme' (GBM) tumour which is a particularly aggressive and invasive tumour. In particular, with the help of a simple growth model, we demonstrate that the short time required for the recurrence of a GBM tumour after a gross total resection cannot be deduced solely from a mutation-based theory. We propose that the transition to invasive tumour phenotypes can be explained on the basis of the microscopic 'Go or Grow' mechanism (migration/proliferation dichotomy) and the oxygen shortage, i.e. hypoxia, in the environment of a growing tumour. We test this hypothesis with the help of a lattice-gas cellular automaton. Finally, we suggest possible therapies that could help prevent the progression towards malignancy and invasiveness of benign tumours.