The exposure of breast cancer cells to fulvestrant and tamoxifen modulates cell migration differently.
There is no doubt that there are increased benefits of hormonal therapy to breast cancer patients; however, current evidence suggests that estrogen receptor (ER) blockage using antiestrogens is associated with a small induction of invasiveness in vitro. The mechanism by which epithelial tumor cells escape from the primary tumor and colonize to a distant site is not entirely understood. This study investigates the effect of two selective antagonists of the ER, Fulvestrant (Fulv) and Tamoxifen (Tam), on the invasive ability of breast cancer cells. We found that 17 β -estradiol (E2) demonstrated a protective role regarding cell migration and invasion. Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression. Furthermore, both tested agents increased expression of matrix metalloproteinases (MMPs) and enhanced invasive potential of breast cancer cells. These changes were in line with focal adhesion kinase (FAK) rearrangement. Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events. Although Fulv caused a less aggressive result compared to Tam, the benefits of hormonal therapy concerning invasion and metastasis yet remain to be investigated.
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, 26504 Rio, Greece.
Dionysia
D
Lymperatou
Efstathia
E
Giannopoulou
Angelos K
AK
Koutras
Haralabos P
HP
Kalofonos
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects*
D015820:Cadherins; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol