Targeting Toll-like receptor 4 with CLI-095 (TAK-242) enhances the antimetastatic effect of the estrogen receptor antago
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RESEARCH ARTICLE
Targeting Toll‑like receptor 4 with CLI‑095 (TAK‑242) enhances the antimetastatic effect of the estrogen receptor antagonist fulvestrant on non‑small cell lung cancer S. Fan1 · Y. Liao2 · W. Qiu3 · L. Li3 · D. Li3 · X. Cao3 · B. Ai3 Received: 19 December 2019 / Accepted: 4 April 2020 © The Author(s) 2020
Abstract Purpose Estrogen plays a critical role in the invasiveness and metastasis of non-small cell lung cancer (NSCLC) through estrogen receptor β (ERβ). However, the antimetastatic effect of the ERβ antagonist fulvestrant was still limited in NSCLC patients. Recently, Toll-like receptor 4 (TLR4) signaling was implicated in NSCLC metastasis. Our present study aimed to evaluate the synergistic antimetastatic effect of a combination of fulvestrant and the TLR4-specific inhibitor CLI-095 (TAK-242) on human NSCLC cells. Methods The expression levels of ERβ and TLR4 were detected by immunohistochemical (IHC) analysis of 180 primary NSCLC and 30 corresponding metastatic lymph node samples. The association between ERβ and TLR4 expression was analyzed. The aggressiveness of NSCLC cells treated with fulvestrant, CLI-095 or the drug combination and formation status of their invadopodia, invasion-associated structures, were investigated. The protein levels in NSCLC cells in different groups were determined by Western blot and immunofluorescence analyses. Results Here, a positive correlation between ERβ and TLR4 expression was observed in both primary NSCLC tissue (Spearman’s Rho correlation coefficient = 0.411, p
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