Estrogen adversely affects the prognosis of patients with lung adenocarcinoma.
Bottom Line: We found that the premenopausal patients had more advanced disease and a shorter survival among the never-smoking female patients with lung adenocarcinoma.We proposed a different pathway that estrogen upregulated the expression of osteopontin and then promoted cell migration through αvβ3 integrin binding and activated MEK-ERK signaling pathway, which is a common downstream pathway with epidermal growth factor receptor (EGFR) activation.An additive effect of ER antagonists and EGFR antagonists on the inhibition of cell migration was also noted.
Affiliation: Division of Pulmonary and Critical Care Medicine, Sun Yat-Sen Cancer Center, Taipei, Taiwan; Department of Medicine, National Yang-Ming University Medical School, Taipei, Taiwan.Show MeSH
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Mentions: To investigate whether the cell-free supernatants of malignant pleural effusions provide a migratory niche for A549 or PE089 cells, the cells were incubated with the malignant pleural effusions from patients with lung adenocarcinoma (n = 24). In Figure5a, the wound healing assays were treated with the malignant pleural effusion from a female never-smoker patient with lung adenocarcinoma harboring an EGFR exon 21 L858R mutation. We found that the malignant pleural effusions more intensely promoted cell migration than E2 or EGF. Additive inhibition of the malignant pleural effusion-induced cell migration was found with tamoxifen and gefitinib supplementations (Fig.5a,b). Patients with malignant pleural effusion had higher pleural fluid E2 (median, 13.0 vs 10.0 pg/mL; P = 0.085) and OPN (median, 318.77 vs 256.28 ng/mL; P = 0.289) concentrations than those with non-malignant pleural effusion, although statistical significance was not reached. The premenopausal women had higher pleural fluid E2 (median, 21.5 vs 13.0 pg/mL; P = 0.044) concentrations than the postmenopausal women. Pleural fluid E2 and OPN concentrations were positively correlated (n = 62, r = 0.74, P = 0.002; Fig.5c).
Affiliation: Division of Pulmonary and Critical Care Medicine, Sun Yat-Sen Cancer Center, Taipei, Taiwan; Department of Medicine, National Yang-Ming University Medical School, Taipei, Taiwan.