Complex 3D Models to Study Drug Targeting of Invadopodia

Njainday   Pulo   Jobe; Daniel      Rosel; Ondrej      Tolde; Jan      Kosla; Jan      Brabek

Abstract

Metastasis is the main cause of death in cancer patients, and in spite of its significance, it is still incompletely understood. In order for cancer to be metastatic, it must undergo a sequence of events, termed as the metastatic cascade. The ability of cancer cells to migrate and invade surrounding tissue is a critical step in the metastasis and is often associated with the formation of specific cellular structures called invadopodia. Invadopodia are actin-based protrusions of tumour cells or transformed cells critically involved in protease secretion and targeting, and cytoskeletal rearrangements enabling cellular invasion. Anti-invadopodia therapy is a possible new field in anti-metastatic treatment. We propose here a novel model for drug discovery of anti-invadopodial compounds based on large scale screening of invadopodia formation in 2D setting followed by validation of the results in complex 3D matrices such as dermis-based matrix.

Keywords: Cancer, drug development, invadopodia, invasiveness, metastasis, 3D, dermis-based matrices.