Previous findings indicated that the activated leukocyte cell adhesion mol. (ALCAM) is expressed by tumors and plays a role in tumor biol. In this study, we show that ALCAM is shed from epithelial ovarian cancer (EOC) cells in vitro, leading to the generation of a sol. ALCAM (sALCAM), consisting of most of the extracellular domain. A similar sALCAM mol. 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. Pharmacol. 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 mol. was expressed in EOC cell lines and ADAM17/TACE silencing by specific small interfering RNA-reduced ALCAM shedding. In addn., 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

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

ROSSELLO, ARMANDO;
2007-01-01

Abstract

Previous findings indicated that the activated leukocyte cell adhesion mol. (ALCAM) is expressed by tumors and plays a role in tumor biol. In this study, we show that ALCAM is shed from epithelial ovarian cancer (EOC) cells in vitro, leading to the generation of a sol. ALCAM (sALCAM), consisting of most of the extracellular domain. A similar sALCAM mol. 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. Pharmacol. 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 mol. was expressed in EOC cell lines and ADAM17/TACE silencing by specific small interfering RNA-reduced ALCAM shedding. In addn., 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
2007
Rosso, Ombretta; Piazza, Tiziana; Bongarzone, Italia; Rossello, Armando; Mezzanzanica, Delia; Canevari, Silvana; ORENGO ANNA, Maria; Puppo, Andrea; Fe...espandi
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/116672
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 42
  • Scopus 94
  • ???jsp.display-item.citation.isi??? 85
social impact