Abstract
Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The controversy is generated by the different premises that researchers adopt to integrate the vast amount of data collected at different levels of biological organization. The so-far hegemonic theory of cancer and its metastases has been the somatic mutation theory (SMT) and a number of its variants: They consider that cancers and their metastases represent a cell-based, genetic and molecular disease. This interpretation has been challenged by the tissue organization field theory (TOFT), which considers instead that cancer is a tissue-based disease, akin to development gone awry. In this Commentary, the merits of both theories are compared now in the context of metastases. Based on the epistemological shortcomings of the SMT and the acknowledged failure of therapeutic approaches based on this theory, we conclude that TOFT explains comprehensibly carcinogenesis and the appearance of metastases.