Targeting the tetraspanin CD81 reduces cancer invasion and metastasis
Menée à l'aide de lignées cellulaires de cancer du sein triple négatif et de xénogreffes sur des modèles murins, cette étude met en évidence l'intérêt de cibler la tétraspanine CD81 pour réduire les processus invasif et métastatique
CD81 belongs to the evolutionary conserved tetraspanin family of proteins that form specialized membranal platforms that facilitate a vast array of cellular processes. However, little is known about the consequences of these molecular interactions under normal or pathological conditions. Tetraspanins have no known natural ligands, but ligation by some antibodies induces functional consequences. Here we show that engagement of CD81 with 5A6 halts tumor invasion in vitro and reduces breast cancer metastasis in vivo. Altogether, these finding highlight the role of CD81 in cancer progression.Tetraspanins are an evolutionary conserved family of proteins involved in multiple aspects of cell physiology, including proliferation, migration and invasion, protein trafficking, and signal transduction; yet their detailed mechanism of action is unknown. Tetraspanins have no known natural ligands, but their engagement by antibodies has begun to reveal their role in cell biology. Studies of tetraspanin knockout mice and of germline mutations in humans have highlighted their role under normal and pathological conditions. Previously, we have shown that mice deficient in the tetraspanin CD81 developed fewer breast cancer metastases compared to their wild-type (WT) counterparts. Here, we show that a unique anti-human CD81 antibody (5A6) effectively halts invasion of triple-negative breast cancer (TNBC) cell lines. We demonstrate that 5A6 induces CD81 clustering at the cell membrane and we implicate JAM-A protein in the ability of this antibody to inhibit tumor cell invasion and migration. Furthermore, in a series of in vivo studies we demonstrate that this antibody inhibits metastases in xenograft models, as well as in syngeneic mice bearing a mouse tumor into which we knocked in the human CD81 epitope recognized by the 5A6 antibody.All study data are included in the article and/or supporting information.