title: Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
abstract: Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites 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 patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies.
authors: Department of Hematology, Oncology, Technical University, 81675 Munich, Germany.
authors: Gloria
authors: G
authors: Lutzny
authors: Thomas
authors: T
authors: Kocher
authors: Marc
authors: M
authors: Schmidt-Supprian
authors: Martina
authors: M
authors: Rudelius
authors: Ludger
authors: L
authors: Klein-Hitpass
authors: Andrew J
authors: AJ
authors: Finch
authors: Jan
authors: J
authors: Dürig
authors: Michaela
authors: M
authors: Wagner
authors: Claudia
authors: C
authors: Haferlach
authors: Alexander
authors: A
authors: Kohlmann
authors: Susanne
authors: S
authors: Schnittger
authors: Marc
authors: M
authors: Seifert
authors: Stefan
authors: S
authors: Wanninger
authors: Nadja
authors: N
authors: Zaborsky
authors: Robert
authors: R
authors: Oostendorp
authors: Jürgen
authors: J
authors: Ruland
authors: Michael
authors: M
authors: Leitges
authors: Toni
authors: T
authors: Kuhnt
authors: Yvonne
authors: Y
authors: Schäfer
authors: Benedikt
authors: B
authors: Lampl
authors: Christian
authors: C
authors: Peschel
authors: Alexander
authors: A
authors: Egle
authors: Ingo
authors: I
authors: Ringshausen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D064546:Protein Kinase C beta; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D011493:Protein Kinase C; D064546:Protein Kinase C beta