Lonardo Fulvio, Li Xiaohua, Siddiq Fauzia, Singh Rajendra, Al-Abbadi Moussa, Pass Harvey I, Sheng Shijie
Department of Pathology, Wayne State University School of Medicine, Harper University Hospital and the Karmanos Cancer Institute, 3990 John R, Detroit, MI 48201, USA.
Lung Cancer. 2006 Jan;51(1):31-9. doi: 10.1016/j.lungcan.2005.07.011. Epub 2005 Sep 12.
Maspin, a mammary homologue of Serine Protease Inhibitors, has been shown to inhibit tumor progression and metastasis. Recently, its biological functions have been linked to its subcellular localization. Specifically, a nuclear, opposed to a combined nuclear and cytoplasmic localization has been associated with increased survival in human malignancies, including non-small cell lung cancer (NSCLC). However, it is not known whether transformation affects maspin expression during lung carcinogenesis, and whether its subcellular localization correlates with the morphological features of NSCLC. To address these questions, we studied maspin expression in a model of transformation of bronchial epithelial cells and in resected NSCLC. We found that decreased maspin accompanied chemical transformation of normal immortalized bronchial epithelial cells BEAS 2B. Immunohistochemistry revealed maspin expression to be virtually universal in NSCLC, occurring in 72/77 Adenocarcinoma (ACa), and 46/46 squamous cell carcinoma (SqCCa). SqCCa showed almost exclusively a combined nuclear-cytosolic stain. In contrast, nuclear maspin, but not combined nuclear-cytoplasmic maspin significantly correlated with low histological grade, lower proliferative rate, absence of invasion, and negative p53 stain in ACa. These data support the hypothesis that nuclear localization of maspin may stratify subtypes of NSCLC with favorable clinical-pathological features.
Maspin是丝氨酸蛋白酶抑制剂的乳腺同源物，已被证明可抑制肿瘤进展和转移。最近，其生物学功能与其亚细胞定位有关。具体而言，与核质联合定位相反，核定位与包括非小细胞肺癌（NSCLC）在内的人类恶性肿瘤患者生存率提高相关。然而，尚不清楚在肺癌发生过程中转化是否会影响maspin表达，以及其亚细胞定位是否与NSCLC的形态学特征相关。为了解决这些问题，我们研究了支气管上皮细胞转化模型和切除的NSCLC中maspin的表达。我们发现，正常永生化支气管上皮细胞BEAS 2B的化学转化伴随着maspin表达降低。免疫组织化学显示maspin在NSCLC中几乎普遍表达，在72/77例腺癌（ACa）和46/46例鳞状细胞癌（SqCCa）中均有表达。SqCCa几乎仅显示核质联合染色。相比之下，在ACa中，核maspin而非核质联合maspin与低组织学分级、较低增殖率、无侵袭以及p53染色阴性显著相关。这些数据支持以下假设：maspin的核定位可能对具有良好临床病理特征的NSCLC亚型进行分层。
