Abstract
In non–small cell lung cancer (NSCLC), estrogen significantly promotes NSCLC cell growth via estrogen receptor beta (ERβ). However, the effects by which ERβ contributes to metastasis in NSCLC have not been previously reported. This study aims at defining whether the stimulation of ERβ promotes NSCLC metastasis in vitro and in vivo. Here, Our results showed that estrogen and ERβ agonist enhanced aggressiveness of two lung cancer cell lines (A549 and H1793) and promoted murine lung metastasis formation. ER-inhibitor Fulvestrant treatment or ERβ-knockdown significantly suppressed the migration, invasion and nodule formation of NSCLC cells. The expression level of ERβ 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 ERβ 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 ERβ and matrix-metalloproteinase-2 (MMP-2) were associated. Furthermore, inhibition of ERβ resulted in down-regulation of MMP-2 expression. Taken together, our results demonstrate that activation of ERβ 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 ERβin the treatment of advanced NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) is one of the most prevalent malignant tumors and is the leading cause of cancer-related death worldwide [1]
The expression level of ERβ 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 ERβ were expressed in lymph node compared to primary tumor tissues
When we grouped the samples according to the distinct IHC score, we found that the proportion of patients with lymph nodemetastasis increased with the ERβ IHC score (Figure 1B)
Summary
Non-small cell lung cancer (NSCLC) is one of the most prevalent malignant tumors and is the leading cause of cancer-related death worldwide [1]. Mortality rates in NSCLC patients remain overly high, with the 5-year overall survival rate of only 15%. During the course of disease, metastasis occurs in approximately 40% to 50% of patients with advanced NSCLC, and the survival time is less than 6 months [2, 3]. According to recent epidemiological data, metastatic NSCLC contributes to rising morbidity and increasing mortality. Over 70% of advanced NSCLC patients die from metastatic spread [4]. There is no effective therapeutic target in patients with advanced metastatic lung cancer. Identification of potential therapeutic targets is a priority to prolong the survival of lung cancer patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
