Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt-dependent pathway.
CD47 is a membrane receptor that plays pivotal roles in many pathophysiological processes, including infection, inflammation, cell spreading, proliferation, and apoptosis. We show that activation of CD47 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. CD47 function-blocking antibodies inhibit proliferation of untreated U87 and U373 cells but not normal astrocytes, suggesting that CD47 may be constitutively activated in astrocytoma. CD47 expression levels were similar in our three cell types. CD47 couples to G-proteins in astrocytes and astrocytoma and especially to the Gβγ dimer. Downstream signaling following CD47 activation involves Gβγ dimer-dependent activation of the PI3K/Akt pathway in astrocytoma cells but not in normal astrocytes. This pathway is known to be deregulated in astrocytoma, leading to cell proliferation and enhanced survival signals. Putative PLIC-1 interaction with CD47 in astrocytoma cells but not astrocytes may contribute to the proliferative effect observed upon activation of CD47. Our data indicate that CD47 receptors have a stimulatory role in cell proliferation and demonstrate for the first time that CD47 signals via the PI3K/Akt pathway in cancerous cells but not normal cells.
Université de Strasbourg, CNRS UMR 7213-Pharmacologie, Faculté de Pharmacie, 74 rte du Rhin, Illkirch, France. esick@pharma.u-strasbg.fr
Emilie
E
Sick
Abdelaziz
A
Boukhari
Thérèse
T
Deramaudt
Philippe
P
Rondé
Bernard
B
Bucher
Philippe
P
André
Jean-Pierre
JP
Gies
Kenneth
K
Takeda
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects; D001254:Astrocytoma / Q000473:pathology / Q000503:physiopathology; D001343:Autophagy / Q000502:physiology; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D000906:Antibodies; D051928:CD47 Antigen; C497894:CD47 protein, human; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014316:Tritium; D000242:Cyclic AMP; D051058:Oncogene Protein v-akt; D002118:Calcium; D013936:Thymidine