The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion

As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelia] cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin 11 (All) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, All (10(-6) M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (P < 0.001) and reduced invasion through collagen-, fibronectin- and laminin-coated membranes (P < 0.05). This action was inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist losartan (10(-5) M). The addition of the AT2R inhibitor PD123319 (10(-5) M) to All-treated cells had no significant effect. Semi-quantitative reverse transcriptase-PCR and western blotting revealed that cells treated with All (10(-6) M) expressed lower levels of both integrin alpha 3 and beta 1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that All reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular alpha 3 and beta 1.