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      Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029.

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          Abstract

          Expression of the tetraspanin CO-029 is associated with poor prognosis in patients with gastrointestinal cancer. In a pancreatic tumor line, overexpression of the rat homologue, D6.1A, induces lethally disseminated intravascular coagulation, suggesting D6.1A engagement in angiogenesis. D6.1A-overexpressing tumor cells induce the greatest amount of angiogenesis in vivo, and tumor cells as well as exosomes derived thereof strikingly increase endothelial cell branching in vitro. Tumor cell-derived D6.1A stimulates angiogenic factor transcription, which includes increased matrix metalloproteinase and urokinase-type plasminogen activator secretion, pronounced vascular endothelial growth factor expression in fibroblasts, vascular endothelial growth factor receptor expression, and strong D6.1A up-regulation in sprouting endothelium. Thus, D6.1A initiates an angiogenic loop that, probably due to the abundance of D6.1A in tumor-derived exosomes, reaches organs distant from the tumor. Most importantly, because of the strong D6.1A up-regulation on sprouting capillaries, angiogenesis could be completely inhibited by a D6.1A-specific antibody, irrespective of whether or not the tumor expresses D6.1A. Tetraspanins have been suggested to be involved in morphogenesis. This is the first report that a tetraspanin, CO-029/D6.1A, promotes tumor growth by its capacity to induce systemic angiogenesis that can effectively, and with high selectivity for sprouting endothelium, be blocked by a D6.1A-specific antibody.

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          Author and article information

          Journal
          Cancer Res
          Cancer research
          American Association for Cancer Research (AACR)
          0008-5472
          0008-5472
          Jul 15 2006
          : 66
          : 14
          Affiliations
          [1 ] Department of Tumor Progression and Immune Defence, German Cancer Research Centre, Heidelberg, Germany.
          Article
          66/14/7083
          10.1158/0008-5472.CAN-06-0391
          16849554
          391f2aa0-766f-487b-9c55-f43a21ddeac8
          History

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