Intercellular Signaling in Cancer—the SMT and TOFT Hypotheses, Exosomes, Telocytes and Metastases: Is the Messenger in the Message?

This review examines the current two leading hypotheses relating to cancer neogenesis-the somatic mutation theory (SMT) and the tissue organization field theory (TOFT)-and focuses on four specific issues. What are the details of the process that changes the epigenetic cargo of the exosomes a cell produces when it becomes malignant? Can exosomes produced by a malignant cell induce on their own a metastatic cancer in the target tissue? What is the functional significance of the fact that exosomes from cancer cells carry in their loads segments of genomic DNA bearing cancer-related mutations across the entire spectrum? What is the evolutionary advantage for the organism of the production by its cancer cells of exosomes that carry epigenetic instructions for the building of elaborate molecular mechanisms that promote the growth of metastatic cancers? These issues are examined with a view of determining the support they give to one or other of the two hypotheses. The conclusion is that they support a specific form of TOFT in which exosomes play a key role.