Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis of human leukemia cells.
Wnt signaling enhances cell proliferation and the maintenance of hematopoietic cells. In contrast, cytotoxic ligand Apo2L/TRAIL induces the apoptosis of various transformed cells. We observed that co-culture of human pre-B leukemia cells KM3 and REH with Wnt1- or Wnt3a-producing rat embryonic fibroblasts efficiently suppressed Apo2L/TRAIL-induced apoptosis of the lymphoid cells. This suppression occurs at the early stages of the Apo2L/TRAIL apoptotic cascade and, interestingly, the activation of the Wnt pathway alone in human leukemia cells is not sufficient for their full anti-apoptotic protection. We hypothesize that a stimulus emanating specifically from Wnt1- or Wnt3a-expressing rat fibroblasts is responsible for the observed resistance to Apo2L/TRAIL. This anti-apoptotic signaling was significantly hampered by the inhibition of the MEK1/ERK1/2 or NFkappaB pathways in KM3 and REH cells. Our results imply that paracrine Wnt-related signals could be important for the survival of pre-B cell-derived malignancies.
Doubravská
Lenka
L
Laboratory of Cell and Developmental Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220, Praha 4, Czech Republic.
Símová
Sárka
S
Cermak
Lukas
L
Valenta
Tomás
T
Korínek
Vladimír
V
Andera
Ladislav
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors*; D051153:Wnt Proteins / Q000096:biosynthesis*; D051155:Wnt1 Protein / Q000096:biosynthesis*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C555510:WNT3A protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D003609:Dactinomycin; D003513:Cycloheximide