Protein Kinase C-
Menée in vitro, in vivo et sur des échantillons prélevés sur des patients atteints d'une leucémie lymphocytaire chronique, d'une leucémie lymphoblastique aiguë ou d'un lymphome à cellules du manteau, cette étude met en évidence le rôle joué par l'expression du gène PKC-
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)-
β
II and the subsequent activation of NF-
κ
B 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-
β
II-NF-
κ
B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-
β
II 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.
º Malignant B cells induce the expression of PKC-
β
II in bone marrow stromal cells
º The activation of NF-
κ
B in tumor stromal cells strictly depends on PKC-
β
II
º The PKC-
β
II-NF-
κ
B pathway is indispensable for survival of malignant B cells in vivo
º The PKC-
β
II-NF-
κ
B pathway is activated by ALL and mantle cell lymphoma cells
Cancer cell , article en libre accès, 2012