Targeting CD13 (aminopeptidase-N) in turn downregulates ADAM17 by internalization in acute myeloid leukaemia cells
| Autor: | Sandrine Bouchet, Fanny Fava, O. Legrand, Ruoping Tang, Brigitte Bauvois |
|---|---|
| Přispěvatelé: | Mort cellulaire et résistance aux traitements dans les hémopathies malignes (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Bauvois, Brigitte, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) |
| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Myeloid [SDV]Life Sciences [q-bio] CD33 myeloid leukaemia hemic and lymphatic diseases Aged 80 and over U937 cell U937 Cells Transfection Middle Aged [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Endocytosis [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences [SDV] Life Sciences [q-bio] Gene Expression Regulation Neoplastic Leukemia Myeloid Acute Leukemia a disintegrin and metalloproteinase Phenotype medicine.anatomical_structure Oncology Female RNA Interference Research Paper Adult matrix metalloproteinase Adolescent medicine.drug_class Down-Regulation HL-60 Cells ADAM17 Protein CD13 Antigens Biology Monoclonal antibody Gene Expression Regulation Enzymologic Young Adult Downregulation and upregulation oncogenesis medicine tumour necrosis factor-α-converting enzyme Humans Aged medicine.disease Molecular biology ADAM Proteins Cell culture Cancer research |
| Zdroj: | Scopus-Elsevier Oncotarget Oncotarget, Impact journals, 2014, 5 (18), pp.8211-8222. ⟨10.18632/oncotarget.1788⟩ Oncotarget, 2014, 5 (18), pp.8211-8222. ⟨10.18632/oncotarget.1788⟩ |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.1788 |
| Popis: | International audience; Secreted matrix metalloproteinases (MMP)-2 and MMP-9 and membrane-anchored aminopeptidase-N/CD13 are abnormally expressed in human acute myeloid leukaemia (AML). We previously showed that CD13 ligation by anti-CD13 monoclonal antibodies can induce apoptosis in AML cells. Here, we assessed ADAM17 expression in primary blood blasts CD13+CD33+ from patients with AML. Primary AML cells expressed ADAM17 transcript and its surface expression was higher in subtype M4 (myelomonocytic) and M5 (monocytic) AML specimens than in M0 and M1/M2 (early and granulocytic) specimens. In AML cell lines defining distinct AML subfamilies (HL-60/M2, NB4/M3, THP-1/M5, U937/M5) and primary AML cells cultured ex vivo, anti-CD13 antibodies downregulated surface CD13 and ADAM17 without affecting MMP-2/-9 release. Knockdown of CD13 by siRNA prevented anti-CD13-mediated ADAM17 downregulation, indicating that CD13 is required for ADAM17 downregulation. Soluble ADAM17 was not detected in the medium of anti-CD13 treated cells, suggesting that ADAM17 was not shed. After ligation by anti-CD13, CD13 and ADAM17 were internalized. Subsequently, we found that ADAM17 interacts with CD13. We postulate that the interaction of ADAM17 with CD13 and its downregulation following CD13 engagement has important implications in AML for the known roles of ADAM17 in tumour-associated cell growth, migration and invasion. |
| Databáze: | OpenAIRE |
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