The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells

Ombretta Rosso, Tiziana Piazza, Italia Bongarzone, Armando Rossello, Delia Mezzanzanica, Silvana Canevari, Anna Maria Orengo, Andrea Puppo, Silvano Ferrini, Marina Fabbi

Research output: Contribution to journalArticlepeer-review

Abstract

Previous findings indicated that the activated leukocyte cell adhesion molecule (ALCAM) is expressed by tumors and plays a role in tumor biology. In this study, we show that ALCAM is shed fromepithelial ovarian cancer (EOC) cells in vitro, leading to the generation of a soluble ALCAM (sALCAM), consisting of most of the extracellular domain. A similar sALCAM molecule was also found in the ascitic fluids and sera from EOC patients, suggesting that this process also occurs in vivo. sALCAM is constitutively produced by EOC cells, and this process can be enhanced by cell treatment with pervanadate, phorbol 12-myristate 13-acetate (PMA), or epidermal growth factor (EGF), a known growth factor for EOC. Pharmacologic inhibitors of matrix metalloproteinases (MMP) and of a disintegrin and metalloproteases (ADAM), and the tissue inhibitor of metalloproteinase-3, significantly inhibited sALCAM release by EOC cells. The ADAM17/TACE molecule was expressed in EOC cell lines and ADAM17/TACE silencing by specific small interfering RNA-reduced ALCAM shedding. In addition, inhibitors of ADAM function blocked EOC cell motility in a wound-healing assay. Conversely, a recombinant antibody blocking ALCAM adhesive functions and inducing ALCAM internalization enhanced EOC cell motility. Altogether, our data suggest that the disruption of ALCAM-mediated adhesion is a relevant step in EOC motility, and ADAM17/TACE takes part in this process, which may be relevant to EOC invasive potential.

Original languageEnglish
Pages (from-to)1246-1253
Number of pages8
JournalMolecular Cancer Research
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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