Cancer: tissue morphogenesis gone awry

30 October 2009

Ana M Soto
Tufts University School of Medicine and
University of Ulster at Coleraine


For almost a century, the somatic mutation theory (SMT) has been the prevalent theory to explain "sporadic" cancers. The SMT posits that the accumulation of mutations in the genome of a single normal cell is responsible for the transformation of such cell into a tumor. This theory regards cancer as a cell-based disease and claims that the default state of cells in metazoan is quiescence. In 1999, we proposed a competing theory, the tissue organization field theory (TOFT). It posits that cancer is a tissue-based disease whereby carcinogens alter normal interactions between the stroma and adjacent epithelium [1]. For the TOFT, the default state of all cells is proliferation, a premise that is relevant and compatible with evolutionary theory. Increasingly, evidence is strengthening this theory.

We consider multicellular organisms as complex systems in which the relations among their parts are contextual and interdependent. We argue that this context-dependence is an effect of diachronic emergence. This reciprocity makes it difficult to establish detailed cause and effect relationships [2]. Thus, hierarchical levels are entangled, precluding at times experimentally isolated cells from revealing their full role in situ in the originating organism. One of the reasons for this outcome is the generation of mechanical forces within the tissue. These mechanical forces are due to a) the adhesion between cells, b) the adhesion between cells and the extracellular matrix that surrounds them, and c) the global properties of the tissue itself (ie, rigidity, elasticity, viscosity). These mechanical forces shape the tissue and even determine cellular fates. In this talk, we will discuss a) how the integration of physical parameters are contributing to the understanding of organogenesis and carcinogenesis and b) the use of mathematical modeling and computer simulation for the analysis of normal and neoplastic development [3].


  1. C Sonnenschein, A M Soto, "Theories of carcinogenesis: an emerging perspective", Sem Cancer Biol 18:372-7 2008. PubMed
  2. A M Soto, C Sonnenschein, P A Miquel, "On physicalism and downward causation in developmental and cancer biology", Acta Biotheor, 56:257-74 2008. PubMed
  3. S G Baker, A M Soto, C Sonnenschein, A Cappuccio, J D Potter, B S Kramer, "Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats", BMC Cancer 9:89 2009. PubMed

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