Clinical & Experimental Metastasis

, Volume 25, Issue 6, pp 665–677

Clonal diversity in carcinomas: its implications for tumour progression and the contribution made to it by epithelial-mesenchymal transitions

  • J. Guy Lyons
  • Erwin Lobo
  • Anna M. Martorana
  • Mary R. Myerscough
Research Paper

DOI: 10.1007/s10585-007-9134-2

Cite this article as:
Lyons, J.G., Lobo, E., Martorana, A.M. et al. Clin Exp Metastasis (2008) 25: 665. doi:10.1007/s10585-007-9134-2


The progression of tumours to malignancy is commonly considered to arise through lineal evolution, a process in which mutations conferring pro-oncogenic cellular phenotypes are acquired by a succession of ever-more dominant clones. However, this model is at odds with the persistent polyclonality observed in many cancers. We propose that an alternative mechanism for tumour progression, called interclonal cooperativity, is likely to play a role at stages of tumour progression when mutations cause microenvironmental changes, such as occur with epithelial-mesenchymal transitions (EMTs). Interclonal cooperativity occurs when cancer cell–cancer cell interactions produce an emergent malignant phenotype from individually non-malignant clones. In interclonal cooperativity, the oncogenic mutations occur in different clones within the tumour that complement each other and cooperate in order to drive progression. This reconciles the accepted genetic and evolutionary basis of cancers with the observed polyclonality in tumours. Here, we provide a conceptual basis for examining the importance of cancer cell–cancer cell interactions to the behaviour of tumours and propose specific mechanisms by which clonal diversity in tumours, including that provided by EMTs, can drive the progression of tumours to malignancy.


Epithelial-mesenchymal transitionClonalityTumour progressionInvasionMetastasisMathematical modelInterclonal cooperativity



Extracellular matrix


Epithelial-mesenchymal transition

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • J. Guy Lyons
    • 1
    • 2
  • Erwin Lobo
    • 3
  • Anna M. Martorana
    • 4
    • 5
  • Mary R. Myerscough
    • 3
  1. 1.Sydney Head & Neck Cancer InstituteSydney Cancer Centre, Royal Prince Alfred HospitalCamperdownAustralia
  2. 2.Dermatology Research LaboratoriesCentral Clinical School, University of SydneySydneyAustralia
  3. 3.School of Mathematics and StatisticsUniversity of SydneySydneyAustralia
  4. 4.University of TechnologySydneyAustralia
  5. 5.Kanematsu Laboratories, Sydney Cancer CentreRoyal Prince Alfred HospitalCamperdownAustralia