Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia.
The biologic effects of recombinant tumor necrosis factor-alpha (rTNF-alpha) and the expression of specific TNF membrane receptors on isolated neoplastic B cells from previously untreated patients with chronic lymphocytic leukemia (CLL) were investigated in vitro. Isolated B cells were incubated up to six days with various concentrations of rTNF-alpha (0.1 to 100 ng/mL). B cells from most patients proliferated ranged from two to 104 times that of unstimulated cells from the same patients. An optimal proliferative effect was achieved at 25 ng/mL rTNF-alpha and an incubation time between 96 and 120 hours, whereas a low concentration of rTNF-alpha (1 ng/mL) reduced [3H]TdR incorporation in four cases. Metaphase cells were detected in the rTNF-alpha-stimulated cultures that proliferated in response to rTNF-alpha. B cells from three of ten patients proliferated spontaneously and proliferation was further enhanced in two patients by rTNF-alpha. TNF binding assays gave a value of approximately 390 to 1,400 binding sites/cell for TNF and a dissociation constant (kd) of approximately 60 pmol/L. These data indicate that rTNF-alpha, in contrast to its cytotoxic/cytostatic effects, can also induce proliferation of tumor cells.
Digel
W
W
Department of Internal Medicine III, University of Ulm, FRG.
Stefanic
M
M
Schöniger
W
W
Buck
C
C
Raghavachar
A
A
Frickhofen
N
N
Heimpel
H
H
Porzsolt
F
F
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D006133:Growth Substances; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013936:Thymidine