SPARC MODULATES MELANOMA CELL - ECM

SALVATIERRA, EE; ALVAREZ, MJ; PODHAJCER, OL

Rosario

Congreso; SAIB; 2006

Cancer progression is characterized by the dynamic interaction of the malignant cell?s cytoskeleton with the extracellular matrix (ECM). SPARC is a secreted non-structural protein component of the ECM, with a yet unclear role in its physiology. However, it has been postulated that SPARC might act as a de-adhesive protein promoting focal cell-adhesion disruption in normal cells. Data from different groups have demonstrated that SPARC expression is associated with aggressive behavior in most human carcinomas. Here we show that knocking-down SPARC expression in melanoma cells using different approaches induced a cytoskeletal rearrangement that was accompanied by relocalization of focal cell adhesion contacts and changes in integrins expression. Moreover, this effect was reversed either by the expression of plasmidic and adenoviral vector-encoded SPARC, or by addition of SPARC protein purified from melanoma. In order to define whether specific members of the Rho small GTPases family are involved in SPARC-induced cytoskeletal rearrangement, we constitutively expressed either their constitutively active or dominant negative forms in SPARCdepleted melanoma cells. Here we show that Rac could act as a potential downstream mediator of SPARC effects on melanoma cells. These results suggest that SPARC enhances melanoma aggressiveness by signalling through specific integrins and small GTPases.