RRC ID 19252
著者 Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jäger U, Gandhi V, Kay NE, Plunkett W, Burger JA.
タイトル Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance.
ジャーナル Blood
Abstract Marrow stromal cells (MSCs) provide important survival and drug resistance signals to chronic lymphocytic leukemia (CLL) cells, but current models to analyze CLL-MSC interactions are heterogeneous. Therefore, we tested different human and murine MSC lines and primary human MSCs for their ability to protect CLL cells from spontaneous and drug-induced apoptosis. Our results show that both human and murine MSCs are equally effective in protecting CLL cells from fludarabine-induced apoptosis. This protective effect was sustained over a wide range of CLL-MSC ratios (5:1 to 100:1), and the levels of protection were reproducible in 4 different laboratories. Human and murine MSCs also protected CLL cells from dexamethasone- and cyclophosphamide-induced apoptosis. This protection required cell-cell contact and was virtually absent when CLL cells were separated from the MSCs by micropore filters. Furthermore, MSCs maintained Mcl-1 and protected CLL cells from spontaneous and fludarabine-induced Mcl-1 and PARP cleavage. Collectively, these studies define common denominators for CLL cocultures with MSCs. They also provide a reliable, validated tool for future investigations into the mechanism of MSC-CLL cross talk and for drug testing in a more relevant fashion than the commonly used suspension cultures.
巻・号 114(20)
ページ 4441-50
公開日 2009-11-12
DOI 10.1182/blood-2009-07-233718
PII S0006-4971(20)38926-6
PMID 19762485
PMC PMC4081374
MeSH Animals Antineoplastic Agents / pharmacology Apoptosis / drug effects Apoptosis / physiology Blotting, Western Bone Marrow Cells / cytology Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism* Cell Adhesion / physiology Cell Communication / physiology* Cell Line, Tumor Cells, Cultured Coculture Techniques Drug Resistance, Neoplasm* Flow Cytometry Humans Leukemia, Lymphocytic, Chronic, B-Cell / metabolism* Leukemia, Lymphocytic, Chronic, B-Cell / pathology Mice Stromal Cells / cytology Stromal Cells / drug effects Stromal Cells / metabolism*
IF 17.794
引用数 222
WOS 分野 HEMATOLOGY
リソース情報
ヒト・動物細胞 KUSA-H1(RCB1990) ST2(RCB0224) KUM4(RCB2112)