PDF(Pubmed)
Abstract：
The ectodomain of the transmembrane protein E-cadherin can be cleaved and released in a soluble form referred to as soluble E-cadherin, or sE-cad, accounting for decreased E-cadherin levels at the cell surface. Among the proteases implicated in this cleavage are matrix metalloproteases (MMP), including MMP9. Opposite functions have been reported for full-length E-cadherin and sE-cad. In this study, we found increased MMP9 levels in the media of two non-small cell lung cancer (NSCLC) cell lines, A549 and H1299, treated with BDNF, nicotine, or epinephrine that were decreased upon cell treatment with the β-adrenergic receptor blocker propranolol. Increased MMP9 levels correlated with increased sE-cad levels in A549 cell media, and knockdown of MMP9 in A549 cells led to downregulation of sE-cad levels in the media. Previously, we reported that A549 and H1299 cell viability increased with nicotine and/or BDNF treatment and decreased upon treatment with propranolol. In investigating the function of sE-cad, we found that immunodepletion of sE-cad from the media of A549 cells untreated or treated with BDNF, nicotine, or epinephrine reduced activation of EGFR and IGF-1R, decreased PI3K and ERK1/2 activities, increased p53 activation, decreased cell viability, and increased apoptosis, while no effects were found using H1299 cells under all conditions tested.
摘要：
跨膜蛋白E-钙粘蛋白的胞外域可以被切割并以可溶性形式释放，称为可溶性E-钙粘蛋白。或者sE-cad，解释细胞表面E-cadherin水平降低。在这种切割中涉及的蛋白酶是基质金属蛋白酶（MMP），包括MMP9。已经报道了全长E-cadherin和sE-cad的相反功能。在这项研究中,我们发现两种非小细胞肺癌（NSCLC）细胞系的培养基中MMP9水平升高，A549和H1299，用BDNF处理，尼古丁,或肾上腺素在用β-肾上腺素能受体阻滞剂普萘洛尔治疗后减少。MMP9水平升高与A549细胞培养基中sE-cad水平升高相关，A549细胞中MMP9的敲除导致培养基中sE-cad水平的下调。以前,我们报道,A549和H1299细胞活力随着尼古丁和/或BDNF的治疗而增加,而随着普萘洛尔的治疗而降低.在研究sE-cad的功能时，我们发现未处理或用BDNF处理的A549细胞培养基中sE-cad的免疫耗竭，尼古丁,或肾上腺素降低EGFR和IGF-1R的激活，PI3K和ERK1/2活性降低，增加p53激活，细胞活力下降，和增加细胞凋亡，而在所有测试条件下使用H1299细胞均未发现影响。
