Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo (Articolo in rivista)

Type
Label
  • Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Rosano L, Spinella F, Di Castro V, Nicotra MR, Albini A, Natali PG, Bagnato A. (2002)
    Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Rosano L, Spinella F, Di Castro V, Nicotra MR, Albini A, Natali PG, Bagnato A. (literal)
Pagina inizio
  • 753 (literal)
Pagina fine
  • 762 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 163 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo (literal)
Abstract
  • Endothelin-1 (ET-1) and its receptors are overexpressed in human Kaposi's sarcoma lesions. Here we show that in human KS IMM cell line ET-1 increased secretion and activation of matrix-metalloproteinase-2 (MMP-2), -3, -7, -9 and -13, as well as of membrane-type 1-MMP (MT1-MMP). ET-1 and ET-3 also enhanced the expression of tissue inhibitor of MMP-2, essential for MT1-MMP-mediated MMP-2 activation. Combined addition of both ET(B) receptor (ET(B)R) and ET(A)R antagonists completely blocked the ET-1-induced MMP activity. By immunohistochemistry, we observed that ET-1 increased MMP-2 and MT1-MMP expression and their localization at the cell surface. Treatment with both antagonists resulted also in the suppression of ET-1-induced phosphorylation of focal adhesion proteins, FAK and paxillin, which are essentials for cell motility. ET-1 induced a dose-dependent enhancement in KS IMM cell migration and MMP-dependent molecule, A-182086, an orally bioavailable ET(A/B)R antagonist, completely inhibited cell proliferation and tumor growth in KS IMM xenografts. These findings demonstrate that ET-1-driven autocrine loop is crucial for enhanced invasiveness of KS IMM cells and promote tumor growth in vivo. Such activities can be blocked by the ET(A/B)R antagonists, which may be effective anti-angiogenic and anti-tumor molecules for the treatment of Kaposi's sarcoma. (literal)
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