Transforming growth factor-␤ (TGF-␤) has multiple functions including increasing extracellular matrix deposition in fibrosis. It functions through a complex family of cell surface receptors that mediate downstream signaling. We report here that a transmembrane heparan sulfate proteoglycan, syndecan-2 (S2), can regulate TGF-␤ signaling. S2 protein increased in the renal interstitium in diabetes and regulated TGF-␤-mediated increased matrix deposition in vitro. Transfection of renal papillary fibroblasts with S2 or a S2 construct that has a truncated cytoplasmic domain (S2⌬S) promoted TGF-␤ binding and S2 core protein ectodomain directly bound TGF-␤. Transfection with S2 increased the amounts of type I and type II TGF-␤ receptors (T␤RI and T␤RII), whereas S2⌬S was much less effective. In contrast, S2⌬S dramatically increased the level of type III TGF-␤ receptor (T␤RIII), betaglycan, whereas S2 resulted in a decrease. Syndecan-2 specifically co-immunoprecipitated with betaglycan but not with T␤RI or T␤RII. This is a novel mechanism of control of TGF-␤ action that may be important in fibrosis.

Multidisciplinary therapy of ENB should be considered, especially for Kadish C and high-grade lesions. Craniofacial resection (CFR), Intensity modulated radiation therapy (IMRT), and chemotherapy should be investigated in a multi-institution trial of ENB.

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Novel strategies targeting human herpesvirus-8, which is present in all cases of Kaposi's sarcoma and primary effusion lymphoma, provide opportunities for selectively killing tumor cells.