Pleiotropic Signal Transduction Mediated by Human CD30: A Member of the Tumor Necrosis Factor Receptor (TNFR) Family

CD30, a member of the tumor necrosis factor receptor (TNFR) family, is a characteristic cell surface receptor for activated T-cells and the malignant cells of Hodgkin's disease (HD), anaplastic large cell lymphoma (ALCL) and a few other non-Hodgkin's lymphomas. As an independent predictor of disease progression and poor prognosis, high serum levels of soluble CD30 (sCD30) have prognostic significance for patients with CD30-positive lymphomas and viral infections. Activation of CD30 by ligand binding or cross-linking with immobilized antibody leads to trimerization of the receptor, recruitment of signaling proteins and transducing of numerous effects. Due to the lack of an intrinsic enzymatic domain, signal transduction is exclusively mediated by the members of the TNFR-associated factor (TRAF) family and the various TRAF-binding proteins. CD30 signaling can induce several pathways including the activation of NF κ B and the MAP kinases. CD30 mediated signal transduction is capable of promoting cell proliferation and cell survival as well as antiproliferative effects and cell death depending on cell type and co-stimulatory effects. Some data indicate the opposite signaling of CD30 in HD or ALCL cells, while other information point to pleiotropic signaling pathways in both malignancies. The pro and contra of this controversy is discussed in this review.