Background: Estrogen has been postulated to contribute to the development and progression of non-small cell lung cancer. It’s also recognized that osteopontin (OPN) plays an important role in tumor progression and metastasis. We explored the characteristics of estrogen, and investigated the connections between estrogen and OPN in lung cancer cells migration, including the signaling pathway involved. The separate and combined effect of Tamoxifen - an estrogen receptor (ER) antagonist, and Ge tinib - an epidermal growth factor receptor (EGFR) antagonist, on the cancer cell migration were also studied.Methods: A549 and PE089 lung cancer cell lines were used for in vitro studies. Pleural effusions from patients with lung adenocarcinoma were collected for the measuring of the estrogen and OPN concentrations as well as their impact on lung cancer cell lines.Results: ER- β is the predominant receptor type in lung cancer cell lines. Estrogen promoted cancer cell proliferation, migration, and matrix metalloproteinase 2 activity. Confocal microscopy and Western blotting revealed ER- βtranslocation out of mitochondria and mitochondrial swelling on the stimulation of estrogen. The mitochondrial respiratory complexes were attenuated. Estrogen induced OPN expression. Osteopontin promoted cancer cell migration through ανβ3 integrin binding. Estrogen and OPN concentrations were both elevated and positively correlated in the malignant pleural effusion from patients with lung adenocarcinoma. Estrogen and OPN affected cell migration through activation of MEK-ERK pathway, which is a common downstream pathway of EGFR activation. Synergistic effect of ER antagonist and EGFR antagonist on the inhibition of lung cancer cells migration was noted.Conclusion: Estrogen up-regulates OPN expression and synergy with epidermal growth factor which promote lung cancer cell migration. Estrogen, with its receptor and OPN, has the potential to be a prognosticator and a new therapeutic target in lung cancer. Understanding the receptors status of patients and tumor characteristics could help better direct the selection of targeted treatment.
Date:
2011-06
Relation:
Journal of Thoracic Oncology. 2011 Jun;6(6):S1001-S1002.
