title: An analysis of the role of follicular lymphoma-associated fibroblasts to promote tumor cell viability following drug-induced apoptosis.
abstract: Treatment response of follicular lymphomas (FL) is highly variable. We, therefore, investigated the role of FL cancer-associated fibroblasts (CAFs) on tumor cell viability, in particular in response to treatment with cytotoxic drugs. Stromal cells outgrown from FL patients were characterized and pure CAF populations were co-cultivated with FL cells. To analyze fibroblast-mediated effects, cells in co-culture were treated with ABT-737 and Bortezomib. The adherent cell population was positive for all fibroblastic markers tested and showed increased mRNA-expression of the activation marker FAP. No effect on FL cell viability was noted when co-cultivating them with CAFs. However, stromal cells protected tumor cells from apoptosis in response to cytotoxic treatment. This might be explained by mRNA-induction of ABCC1 and ABCG2 and up-regulation of BCL2L1 in FL cells. Our finding of protective mechanisms mediated by CAFs is of pivotal impact for further studies of cytotoxic agents in FL.
authors.affiliation: a Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , University of Tübingen , Stuttgart , Germany.|b Department of Clinical Pathology , Robert-Bosch-Krankenhaus , Stuttgart , Germany.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Staiger
authors.affiliation: a Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , University of Tübingen , Stuttgart , Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Duppel
authors.affiliation: a Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , University of Tübingen , Stuttgart , Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dengler
authors.affiliation: a Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , University of Tübingen , Stuttgart , Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: van der Kuip
authors.affiliation: c Department of Internal Medicine, Oncology and Hematology , Robert-Bosch-Krankenhaus , Stuttgart , Germany.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Vöhringer
authors.affiliation: c Department of Internal Medicine, Oncology and Hematology , Robert-Bosch-Krankenhaus , Stuttgart , Germany.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Aulitzky
authors.affiliation: d Institute of Pathology , University of Würzburg, Comprehensive Cancer Center Mainfranken (CCCM) , Würzburg , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: b Department of Clinical Pathology , Robert-Bosch-Krankenhaus , Stuttgart , Germany.
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: a Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , University of Tübingen , Stuttgart , Germany.|b Department of Clinical Pathology , Robert-Bosch-Krankenhaus , Stuttgart , Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Horn
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D001713:Biphenyl Compounds / Q000494:pharmacology; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018941:Antigens, CD19; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D015415:Biomarkers; D001713:Biphenyl Compounds; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015260:Neprilysin; D009596:Nitrophenols; D010879:Piperazines; D013449:Sulfonamides; D051020:bcl-X Protein; C501332:ABT-737; C421109:multidrug resistance-associated protein 1
keywords: CD20; Follicular lymphoma; apoptosis; cancer-associated fibroblast; co-cultivation