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Stroma-Initiated Hedgehog Signaling Takes Center Stage in B-Cell Lymphoma

National Center for Tumor Diseases, Department of Translational Oncology G100, Heidelberg, Germany

Requests for reprints: Ralph K. Lindemann, National Center for Tumor Diseases, Department of Translational Oncology G100, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany. Phone: 49-6221-421602; Fax: 49-6221-421611; E-mail: ralph.lindemann{at}nct-heidelberg.de.

Hedgehog-mediated signaling has been shown to promote growth and dissemination of solid cancers, most prominently basal cell carcinomas and medulloblastoma. Recent findings indicate that hedgehog signals are also important for tumor growth in hematologic malignancies. Hedgehog ligands secreted by stromal cells could elicit Patched/Smoothened-mediated antiapoptotic signaling in mouse B-cell lymphomas. Inhibition of hedgehog signaling induced apoptosis in lymphoma cells and prolonged survival of lymphoma-bearing mice. Depletion of tumor cells proceeded in the absence of p53 via the mitochondrial apoptotic pathway. These and other recently published data on hedgehog inhibition in cancer cells and their implications will be discussed. [Cancer Res 2008;68(4):961–4]

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