Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies

We have previously shown that expression of heregulin (HRG) is closely corr elated with breast cancer progression. We have subsequently isolated Cyr61, a ligand fur the alpha (v)beta (3) integrin that is differentially express ed in HRG-positive cells, and have? shown that it is expressed in all of th e invasive and metastatic breast cancer cell lines tested. Preliminary eval uation of Cyr61 expression in breast tumor biopsies revealed expression of Cyr61 in about 30% of invasive breast carcinomas. Significantly, we demonst rated that Cyr61 is a downstream effector of HRG action, because a Cyr61-ne utralizing antibody abolished the ability of HRG-expressing cells to migrat e ill vitro. Furthermore, we have shown that HRG-expressing cells denote hi gher levels of alpha (v)beta (3) expression, and we have established that C yr61 action is mediated, at least in part, through its receptor alpha (v)be ta (3), because a functional blocking antibody of the alpha (v)beta (3) blo cked the Matrigel outgrowth of HRG-expressing cells. These results strongly suggest that Cyr61 is necessary for HRG-mediated chemomigration and that C yr61 plays a functional role in breast cancer progression, possibly through its interactions with the alpha (v)beta (3) receptor.