Irradiated fibroblasts protect Burkitt lymphoma cells from apoptosis by a mechanism independent of bcl-2.
When cells of fresh Burkitt lymphoma (BL) biopsies are explanted into tissue culture, their survival and growth are greatly dependent on the presence of a feeder layer of irradiated fibroblasts. To investigate the nature of this feeder dependence, we characterized the growth requirements of a panel of Epstein-Barr Virus (EBV)-negative and -positive BL cell lines in both the absence and the presence of feeder cells in vitro. Four EBV-negative BL lines and 4 EBV-positive lines displaying the phenotype of BL cells in vivo required high cell density for proliferation in the absence of feeder cells, but grew out as single-cell clones when seeded on irradiated human fibroblasts. EBV-positive BL cell lines which had acquired an activated phenotype similar to that of lymphoblastoid cell lines required much lower cell densities for autonomous proliferation. The EBV-negative Burkitt lymphoma line BL70 was used as a model to study the feeder-cell dependence in more detail. BL70 cells grew in the absence of feeder cells only at high cell density and at high FCS concentration. In the presence of feeder cells, BL70 cells became clonogenic even at greatly reduced FCS concentration. A decrease in either cell density or FCS concentration induced apoptosis. Supernatants from feeder cells and from BL70 cells growing autonomously at high cell density were unable to substitute for the survival and growth-promoting effect of the feeder cells. Protection of Burkitt lymphoma cells from apoptosis by co-cultivation with irradiated fibroblasts was not mediated by induction of bcl-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Institut für Klinische Molekularbiologie und Tumorgenetik, Hämatologikum der GSF, Munich, Germany.
M H
MH
Falk
L
L
Hültner
A
A
Milner
C D
CD
Gregory
G W
GW
Bornkamm
D017209:Apoptosis / Q000502:physiology*; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects*; D004854:Herpesvirus 4, Human; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2