Protein Kinase C-¦Â-Dependent Activation of NF-¦ÊB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In?Vivo

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• 作者：Gloria Lutzny¹ ; Thomas Kocher⁴ ; Marc Schmidt-Supprian⁵ ; Martina Rudelius² ; Ludger Klein-Hitpass⁶ ; Andrew J. Finch⁸ ; ⁹ ; Jan Dü ; rig⁷ ; Michaela Wagner¹ ; Claudia Haferlach¹⁰ ; Alexander Kohlmann¹⁰ ; Susanne Schnittger¹⁰ ; Marc Seifert⁶ ; Stefan Wanninger³ ; Nadja Zaborsky⁴ ; Robert Oostendorp¹ ; Jü ; rgen Ruland³ ; Michael Leitges¹¹ ; Toni Kuhnt¹ ; Yvonne Schä ; fer¹ ; Benedikt Lampl¹ ; Christian Peschel¹ ; Alexander Egle⁴ ; Ingo Ringshausen¹ ; ^{i.ringshausen@lrz.tu-muenchen.de}
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：14 January, 2013
• 年：2013
• 卷：23
• 期：1
• 页码：77-92
• 全文大小：2297 K

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Summary

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)-¦ÂII and the subsequent activation of NF-¦ÊB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-¦Â knockout mice are insusceptible to CLL transplantations, underscoring the in?vivo significance of the PKC-¦ÂII-NF-¦ÊB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-¦ÂII 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.