Population depletion activates autonomous CD154-dependent survival in biopsylike Burkitt lymphoma cells.
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.
Challa
Anita
A
MRC Centre for Immune Regulation and the Institute for Cancer Studies, The University of Birmingham, Birmingham, United Kingdom.
Eliopoulos
Aristides G
AG
Holder
Michelle J
MJ
Burguete
Alondra Schweizer
AS
Pound
John D
JD
Chamba
Anita
A
Grafton
Gillian
G
Armitage
Richard J
RJ
Gregory
Christopher D
CD
Martinez-Valdez
Hector
H
Young
Lawrence
L
Gordon
John
J
D001706:Biopsy; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology*; D023201:CD40 Ligand / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D002450:Cell Communication; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D023201:CD40 Ligand