Background: Physiologic wound repair and tissue regeneration are associated with distinct cellular behaviors triggered by tissue damage. Normally quiescent stem cells proliferate to regenerate damaged tissue, while relatively immobile epithelial cells can transform into a motile, tissue invasive phenotype through a partial epithelial-mesenchymal transition. These distinct cellular behaviors may have particular relevance to how cancer cells can be predicted to behave after treatments damaging a tumor.
Presentation of the hypothesis: Surgery, chemotherapy, and radiation therapy trigger highly conserved wound healing pathways that: (1) facilitate the phenotypic transformation of surviving cancer cells into a highly mobile, metastatic phenotype through an EMT or epithelial-mesenchymal transition and (2) induce residual cancer stem cell proliferation.
Testing the hypothesis: Tissue damage caused by cancer treatments will trigger the release of distinct cytokines with established roles in physiologic wound healing, EMT induction, and stem cell activation. They will be released rapidly after treatment and detectable in the patient's blood. Careful histologic evaluation of cancerous tissue before and after treatment will reveal cellular changes suggestive of EMT induction (down regulation of cytokeratin expression) and cancer stem cell enrichment (stem cell markers upregulated).
Implications of the hypothesis: Cancer cells surviving treatment will be more capable of metastasis and resistant to conventional therapies than the pre-treatment population of cancer cells. These changes will develop rapidly after treatment and, in distinct contrast to selection pressures fostering such changes, be triggered by highly conserved wound repair signals released after tissue damage. This pattern of tissue (tumor) repair may be amenable to treatment intervention at the time it is upregulated.