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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3411-3418
NEOPLASIA
Population depletion activates autonomous CD154-dependent
survival in biopsylike Burkitt lymphoma cells
Anita Challa,
Aristides G. Eliopoulos,
Michelle J. Holder,
Alondra Schweizer Burguete,
John D. Pound,
Anita Chamba,
Gillian Grafton,
Richard J. Armitage,
Christopher D. Gregory,
Hector Martinez-Valdez,
Lawrence Young, and
John Gordon
From the MRC Centre for Immune Regulation and the
Institute for Cancer Studies, The University of Birmingham, Birmingham,
United Kingdom; School of Biomedical Sciences, The University of
Nottingham, Nottingham, United Kingdom; Institute of Cell, Animal and
Population Biology, University of Edinburgh, United Kingdom; Immunex
Corporation, Seattle, WA; Department of Immunology, MD Anderson Cancer
Center, Houston, TX.
Population size is governed through cells reacting to a variety of
intrinsic and extrinsic cues. Tumors, while liberated from many of the
homeostatic constraints placed on physiologic counterparts, can
nonetheless remain subject to both social and environmental control.
Burkitt lymphoma cells faithful to the biopsy phenotype were used to
model the reliance of the colony, if any, on an inbuilt population
sensor. Below a normally suicidal threshold number of cells, low
picomolar quantities of exogenous CD40 ligand (CD40L/CD154) were found to sustain the clone without the discernible shift in
phenotype that accompanies high CD40L encounter. Although CD154 was
undetectable in populous cultures, message was induced as numbers
became limiting. Correspondingly, attempts to neutralize endogenous CD40L activity failed to perturb cells at optimal densities but resulted in their marked decline as the critical threshold was
approached. These data reveal an auto-inducible survival mechanism seemingly regulated through the monitoring of population size, a
process somewhat akin to that of "quorum sensing" among
gram-negative bacteria in which diffusible molecules provide a means of
communication to coordinate gene expression with population density.
This process could be activated as cells discern depletions in
their community or when deprived of signals otherwise furnished within
an appropriate environmental niche.
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