Transforming growth factor-ß1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways.

Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition (EMT), which is a process whereby epithelial cells lose their polarity and acquire new features of mesenchyme. EMT has been reported to be induced by transforming growth factor-ß1 (TGF-ß1), but its mechanism remains elusive. In this study, we performed a study to investigate whether PI3K/Akt and MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549 cells. The results showed that after treated with TGF-ß1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-ß1-induced EMT after 48 h was accompanied by increased of cell migration and change of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-ß1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-ß1-induced EMT of A549 cells.

[Video-assisted thoracic surgery lobectomy versus open lobectomy for mini pathologic N2 non-small cell lung cancer].

OBJECTIVE: To assess early and late outcomes of patients with minimal mediastinal lymph nodes metastasis N2 non-small cell lung cancer disease unexpectedly detected during the operation, who underwent video-assisted thoracic surgery lobectomy for clinical stage I. METHODS: This study retrospectively reviewed and analyzed the medical records of 263 patients underwent surgery between January 2004 and December 2007, who were diagnosed as having early-stage non-small cell lung cancer (clinical stage was cT1-2N0M0, stage I) before the surgery, but were found to have mini mediastinal lymph nodes metastasis disease (clinical stage was pT1-2N2M0, stage IIIa) unexpectedly detected during the operation and after the operation. All patients underwent lobectomy and systematic lymph nodes dissection as radical treatments. Among them, 63 patients underwent video-assisted thoracic surgery (VATS) lobectomy, including 37 male patients (58.7%) with a mean age of (58 ± 11) years old. Two hundred patients underwent open thoracotomy lobectomy, including 132 male patients (66%) with a mean age of (59 ± 11) years old. To compare and analyze clinical features, early and late outcomes of patients in these two groups. RESULTS: A total of 263 patients with an average survival time (34.9 ± 1.2) months (median 31 months), 63 cases in VATS lobectomy group with an average survival time (40.3 ± 2.2) months (median 37 months), 200 cases in open pulmonary lobectomy group with an average survival time (33.1 ± 1.3) months (median 29 months). The 1-, 2-, 3-year over survival rate of all the patients was 92.0%, 57.4%, 29.3%. The 1-, 2-, 3-year survival rate of patients in VATS lobectomy group was 92.1%, 82.5%, 41.3%. The 1, 2, 3 year survival rate of patients in thoracotomy lobectomy group was 92.0%, 49.5%, 25.5%. There was significant difference between the two groups in this factor (χ(2) = 5.58, P = 0.018). CONCLUSIONS: VATS lobectomy is feasibility and safety for unexpected mini N2 disease. Even if lymph node metastasis is unexpectedly detected during video-assisted thoracic surgery lobectomy for clinical stage I disease after rigorous evaluation of preoperative, it is no need to convert to conventional thoracotomy.

Transforming growth factor-ß1 promotes lung adenocarcinoma invasion and metastasis by epithelial-to-mesenchymal transition.

Lung cancer is a highly malignant carcinoma, and most deaths of lung cancer are caused by metastasis. The alterations associated with epithelial-to-mesenchymal transition (EMT) may be related to the cancer cell metastasis. Nevertheless, the mechanism of lung cancer metastasis remains unclear. We conducted a study in vitro to investigate whether transforming growth factor-ß1 (TGF-ß1) could induce changes of, such as cell morphology, expression of relative protein markers, and cellular motile and invasive activities. In this research, the changes of cell morphology were first investigated under a phase contrast microscope, then western blotting was employed to detect the expression of E-cadherin, vimentin, and fibronectin, and finally cell motility and invasion were evaluated by cell wound-healing as well as invasion assays. The data indicated that human lung adenocarcinoma cell lines, A-549 and PC-9 cells of epithelial cell characteristics, were induced to undergo EMT by TGF-ß1. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker E-cadherin and increased mesenchymal markers vimentin and fibronectin. More importantly, cell motility and invasion were also enhanced in the EMT process. These results indicated that TGF-ß1 may promote lung adenocarcinoma invasion and metastasis via the mechanism of EMT.