Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion.
BACKGROUND
Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted.


METHODS
We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17beta-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling.


RESULTS
Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells.


CONCLUSIONS
These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.
Fu
Xiao-Dong
XD
Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, University of Pisa, Pisa 56100, Italy. fuxiaodong27@hotmail.com
Giretti
Maria Silvia
MS
Goglia
Lorenzo
L
Flamini
Marina Ines
MI
Sanchez
Angel Matias
AM
Baldacci
Chiara
C
Garibaldi
Silvia
S
Sitruk-Ware
Regine
R
Genazzani
Andrea Riccardo
AR
Simoncini
Tommaso
T
D000199:Actins / Q000378:metabolism; D000736:Androstenes / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009653:Norprogesterones / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000199:Actins; D000736:Androstenes; D008840:Microfilament Proteins; D009653:Norprogesterones; C071058:moesin; D011374:Progesterone; D004958:Estradiol; C029167:ST 1435; D017258:Medroxyprogesterone Acetate; C035144:drospirenone