Societal Interactions in Ovarian Cancer Metastases: A Quorum Sensing Hypothesis

摘要

It is unknown what specific biochemical and biological mechanisms control metastasis. We pursued the work proposed in this application because it is our assertion that uncovering the mechanism(s) responsible for regulating metastatic colonization in ovarian requires a fresh look from a new perspective. To this end we formulated and began to test a completely novel hypothesis: That a Quorum Sensing mechanism is involved in metastatic colonization. Quorum Sensing is a process of cell-cell communication that bacteria use to control gene expression in response to fluctuations in cell population density. Quorum Sensing involves production of and response to the accumulation of a critical concentration of extracellular signal molecules. This mechanism allows bacteria to act as individuals and participate in group activities. Of relevance to metastasis is the finding that pathogenic bacteria can sense and integrate information about their numbers (quorum) physical interactions with host cells and host-derived stress cytokines. When certain bacteria sense host vulnerability and have sufficient cell density they initiate a coordinated attack by expressing virulence genes and forming organized stable biofilms i.e. complex heterogeneous communities of cells within an extracellular matrix attached to a solid surface which exacerbate disease and are refractory to a battery of therapies. This process is analogous to metastatic colonization in ovarian cancer: cells migrate toward/on target surfaces (organ-specific homing) show cell-cell and cell-matrix interactions (tumor cell-stromal cell crosstalk) remain subclinical until they can mount an effective attack (dormancy) form complex structures with channels for nutrient flow (vascularized lesions) and contain resistant cells which can cause disease recurrence (persistors).