384 - The role of antiestrogens in breast cancer cells’ invasiveness

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Presenter Dionysia Lymperatou
Authors D.V. Lymperatou
  • Department Of Medicine, Division Of Oncology, University Hospital of Patras, 26504 - Patras/GR

Abstract

Aim

The current study investigates the effect of two selective antagonists of the estrogen receptor (ER), fulvestrant (FL) and tamoxifen (Tam), on the invasive ability of breast cancer cells. ER blockage using anti-estrogens is associated with a small induction of invasiveness. Moreover, matrix metalloproteinases (MMPs) contribute to this procedure by cleaving components of the extracellular matrix, forming a path for the migrating cells. In addition, the focal adhesion kinase (FAK) plays a central role in invasiveness.

Methods

We used two ER+ breast cancer cell lines, MCF7 and T47D. Cells were stimulated by estradiol (E2) and then treated with FL, Tam and the metabolites endoxifen (End) and 4OH-tamoxifen (4OHT). The invasiveness was evaluated using the matrigel assay and MMPs expression with gelatin zymography assay. Using immunofluoresence, we study the expression and localization of phospho FAK and its correlation with F-actin.

Results

We found that E2 exerts a protective role in invasiveness. On the contrary, the anti-estrogens, as well as their metabolites reversed the effect of E2, a finding that was more obvious with Tam. The effect of the agents on MMPs expression was more pronounced at 48 h, when Tam and 4OHT were found to reduce the levels of both MMP-2 and MMP-9 compared to FL. Following E2 exposure, the maximum autophosphorylation of FAK (Y397) was observed at 10 min. At the same time point we assessed the effect of our agents, regarding the spatial organization of actin fibers. The concurrent administration of E2 with FL, Tam or End was associated with rearrangement of cytoskeleton, a finding that was not observed in untreated cells, as well as after the use of 4OHT and E2 or E2 alone.

Conclusions

Our results indicate that the metabolite 4OHT is superior to the pro-drug Tam as well as the pure anti-estrogen FL with respect to invasiveness, MMPs induction and actin rearrangement. Regarding the comparison of Tam with FL, the effect on MMPs and rearrangement was similar. However, FL was found to be slightly superior to Tam concerning invasiveness.

Disclosure

All authors have declared no conflicts of interest.