BioProject

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. More...

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-βII and the subsequent activation of NF-κB in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC-β knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-βII- NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII 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) Overall design: 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.. Less...