Societal interactions in ovarian cancer metastasis: a quorum-sensing hypothesis.

Clin Exp Metastasis. 2009;26(1):67-76. Epub 2008 May 31.


The Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL 60637, USA.


The biochemical and biological mechanisms metastatic cancer cells use to function as communities and thwart internal and external growth control mechanisms remain undefined. In this work, we present the hypothesis that cancer cells may use a Quorum-Sensing mechanism to regulate multicellular functions and control steps in metastatic colonization. Quorum sensing is a bacterial cell-cell communication process used to track increasing cell-population density and, in response to changes in cell number, coordinate gene expression and behavior on a community-wide scale. Important parallels between the behavior of societies of bacterial cells and societies of malignant cancer cells exist in the bacterial literature. Of relevance to metastasis is the finding that pathogenic bacteria use quorum sensing to determine when their population numbers are high enough to collectively form biofilms in or on host organisms. Biofilms are complex, heterogeneous communities of bacterial cells encased within an extracellular matrix attached to a solid surface. Biofilms exacerbate disease and are refractory to a battery of therapies. We suggest that thequorum-sensing-controlled bacterial biofilm formation process closely parallels the steps in metastatic colonization. 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). Using ovarian cancer as an example, we present data supporting the connection between metastatic colonization and quorum sensing and discuss the implications for understanding and controlling metastasis formation.

PMID: 18516689
 [PubMed – indexed for MEDLINE]

Link to Full Article

An analogy between the evolution of drug resistance in bacterial communities and malignant tissues.

Lambert GEstévez-Salmeron LOh SLiao DEmerson BMTlsty TDAustin RH.

Nat Rev Cancer. 2011 May;11(5):375-82.


Department of Physics, Princeton University, Princeton, NJ 08544, USA.


Cancer cells rapidly evolve drug resistance through somatic evolution and, in order to continue growth in the metastatic phase, violate the organism-wide consensus of regulated growth and beneficial communal interactions. We suggest that there is a fundamental mechanistic connection between the rapid evolution of resistance to chemotherapy in cellular communities within malignant tissues and the rapid evolution of antibiotic resistance inbacterial communities. We propose that this evolution is the result of a programmed and collective stress response performed by interacting cells, and that, given this fundamental connection, studying bacterial communities can provide deeper insights into the dynamics of adaptation and theevolution of cells within tumours.

 [PubMed – indexed for MEDLINE]

Link to Full Paper