Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines

Abstract

Abstract. Mammary serine protease inhibitor (maspin) is a tumor suppressor gene that is silenced in the majority of cancer cells during metastatic progression by transcriptional and epigenetic mechanisms. The function of maspin in non-small cell lung cancer cells (NSCLC) has not been clearly defined. In the present study, the expression of maspin in NSCLC cell lines, in particular, the adenocarcinoma cell lines, was heterogeneous. While the expression levels of maspin in PC-9 and H460 cell lines were intact, the expression of maspin in the A549 and SPC-A1 cells was hardly detected. Ectopic expression of maspin in A549 cells carrying the K-ras gene point mutation significantly inhibited cell migration and invasion abilities, which was associated with downregulated expression of matrix metalloproteinase-2 and integrin β1. Ectopic expression of maspin in SPC-A1 cells harboring the wild-type K-ras gene predominantly affected cell growth via targeting the AKT signaling molecules. Maspin functions differently in lung adenocarcinoma cells, possibly due to the varied molecular characteristics. IntroductionLung cancer is a leading cause of cancer mortality worldwide. Lung cancer is generally divided into non-small cell lung cancer cells (NSCLC) and SCLC, in which the NSCLC constitutes 80-85% of lung cancers. The three major NSCLC subtypes are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. NSCLC, which is characterized by slow tumor cell growth and dissemination, is refractory to chemotherapy and chest radiotherapy. Several driven genes have been identified in NSCLC, such as EGFR, c-MET and the ALK-EML4 fusion gene (1). Treatment for lung cancer is mainly based on tumor stage, tumor pathology and molecular pathology. Understanding thoroughly the molecular mechanism underlying the aberrant cellular events driving lung cancer progressions is crucial for developing novel treatments.Mammary serine protease inhibitor (maspin), also known as Serpin B5, was first identified in 1994 (2). Maspin belongs to the serine protease inhibitor superfamily, and is predominantly localized in the cytoplasm, but is also localized in the nucleus and membrane, and is secreted. The exact roles of maspin in cancer are far more complicated than initially thought due to the conflicting experimental and clinical data that have been reported. In prostate cancer, the expression of maspin is frequently absent (3). Overexpression of maspin is considered an independent factor in predicting a favorable prognosis in breast cancer and lung squamous cell cancer (4-6). However, it has been also reported that the increased nuclear maspin expression predicts a favorable prognosis, whereas the enhanced cytoplasmic expression is associated with early-relapsing and unfavorable prognosis in breast cancer (7). Enhanced expression of maspin is correlated with unfavorable prognosis in pancreatic, ovarian and colorectal cancer (8-10). High maspin expression correlates with an unfavorable outcome in colorectal cancer in stage III and IV, suggesting th...

Personalized Tumor Growth Prediction Using Multiscale Modeling

“…Tumor growth patterns fit a Gompertzian growth curve, i. e. a sigmoid function (49)(50)(51)(52)(53)(54). Our simulations are also validated by the observation that the tumor growth process can be defined as a sigmoid curve that starts with a high exponential growth rate but eventually levels-off with saturation (see Figure 11).…”

Personalized Tumor Growth Prediction with Multiscale Tumor Modeling

“…Tumor growth patterns fit a Gompertz curve, which is a sigmoid function [30][31][32][33][34][35]. Our simulations are also validated by the observation that the tumor growth process can be defined as a sigmoid curve that starts with a high exponential growth rate but eventually levels-off with saturation (see Figure 7).…”

SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial‐mesenchymal transition (EMT) in lung adenocarcinoma

“…In non‐small cell lung cancer (NSCLC), overexpression of SERPINB5 in the cytoplasm may be a useful indicator of tumor progression 25 . SERPINB5 showed different functions in different lung adenocarcinoma cell lines 26 . Eighty‐five genes related to SERPINB5 were identified by meta‐analysis in NSCLC 27 .…”