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Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system
Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.
Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.ORCID iD: 0000-0001-9518-1411
Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.
Hematology/Oncology, University Children's Hospital and Division of Molecular University Children's Hospital, Prittwitzstr. 43, D-89075 Ulm, Germany.
1998 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 76, no 1, 105-114 p.Article in journal (Refereed) Published
Abstract [en]

We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system, Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')(2) anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis, Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis, The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases, Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors. (C) 1998 Wiley-Liss, Inc.

Place, publisher, year, edition, pages
1998. Vol. 76, no 1, 105-114 p.
Keyword [en]
apo-1, Apoptosis, continuous-infusion, expression, factor receptor superfamily, family, fas ligand, leukemia, member, molecular-cloning
National Category
Cancer and Oncology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-87067DOI: 10.1002/(SICI)1097-0215(19980330)76:1<105::AID-IJC17>3.0.CO;2-BISI: 000072767000018PubMedID: 9533769OAI: oai:DiVA.org:liu-87067DiVA: diva2:584764
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2013-09-03

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Los, Marek Jan
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