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2017 ; 8
(34
): 56443-56459
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Estrogen promotes tumor metastasis via estrogen receptor beta-mediated regulation
of matrix-metalloproteinase-2 in non-small cell lung cancer
#MMPMID28915603
Fan S
; Liao Y
; Liu C
; Huang Q
; Liang H
; Ai B
; Fu S
; Zhou S
Oncotarget
2017[Aug]; 8
(34
): 56443-56459
PMID28915603
show ga
In non-small cell lung cancer (NSCLC), estrogen significantly promotes NSCLC cell
growth via estrogen receptor beta (ER?). However, the effects by which ER?
contributes to metastasis in NSCLC have not been previously reported. This study
aims at defining whether the stimulation of ER? promotes NSCLC metastasis in
vitro and in vivo. Here, Our results showed that estrogen and ER? agonist
enhanced aggressiveness of two lung cancer cell lines (A549 and H1793) and
promoted murine lung metastasis formation. ER-inhibitor Fulvestrant treatment or
ER?-knockdown significantly suppressed the migration, invasion and nodule
formation of NSCLC cells. The expression level of ER? protein was analyzed in
matched samples of metastatic lymph node and primary tumor tissues from the same
individuals, and we found significantly higher levels of ER? were expressed in
lymph node compared to primary tumor tissues. Moreover, Studies on both surgical
biopsies and on lung cancer cells revealed that the expression level of ER? and
matrix-metalloproteinase-2 (MMP-2) were associated. Furthermore, inhibition of
ER? resulted in down-regulation of MMP-2 expression. Taken together, our results
demonstrate that activation of ER? in lung cancer cells promotes tumor metastasis
through increasing expression of invasiveness-associated MMP-2. These results
also highlight the therapeutic potential of inhibition of ER?in the treatment of
advanced NSCLC.
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