Effect of NF-kappaB activation in bone marrow stromal cells co-cultured with CLL cells
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ABSTRACT: Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-M-NM-2II and the subsequent activation of NF-M-NM-:B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC-M-NM-2 knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-M-NM-2II- NF-M-NM-:B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-M-NM-2II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies. We used microarrays to determine Nemo/ IKK-gamma dependent gene expression changes in bone marrow stromal cells (BMSCs) induced by co-culturing with leukemic B-cells (CLL) We compared mouse BMSC cells from Nemo knockout cells (Nemo+CRE) and Nemo wild type cells (Nemo-CRE) co-cultured for 5 days with leukemic B-cells microarray analysis on Affymetrix MG-430_2.0 arrays..
ORGANISM(S): Mus musculus
SUBMITTER: Ludger Klein-Hitpass
PROVIDER: E-GEOD-36415 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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