Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinorna other than bronchioloalveolar carcinoma
Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinorna other than bronchioloalveolar carcinoma
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DOI：
10.1097/01.lab.0000081391.28136.80
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发表时间：
2003-08-01
影响因子：
5
通讯作者：
Kitamura, Y
中科院分区：
文献类型：
--
作者：
Ito, A;Okada, M;Kitamura, Y
TSLC1(肺癌肿瘤抑制因子-1)是免疫球蛋白超家族的一种黏附分子，它以同源亲和性结合并介导细胞间的相互作用。最初，TSLC1是从人类非小细胞肺癌(NSCLC)中经常表现出异质性缺失的基因组区域克隆出来的候选抑癌基因。然而，目前还没有关于TSLC1在正常肺和非小细胞肺癌中表达的研究。在这里，我们发现肺上皮细胞表达TSLC1，其表达水平在非小细胞肺癌的主要组织学类型--原发性肺腺癌中经常降低或消失。免疫组织化学结果显示，在交配后10.5天和13天的小鼠胚胎肺中，TSLC1定位于所有柱状上皮细胞的细胞边界。在成人肺的细支气管和肺泡上皮细胞中观察到类似的染色模式，表明TSLC1在这些细胞的相互作用中具有生理作用。接下来，我们对47例原发性肺腺癌进行了TSLc1的蛋白质印迹分析，通过比较肿瘤和正常肺组织中TSLc1的表达水平，判断每个肿瘤是否降低。表达谱与组织学亚型显著相关，但与其他临床病理参数无关。16例细支气管肺泡癌(BAC)均被判定为无减少，而31例BAG以外的腺癌中有19例(63%)被判定为减少(P<；0.0001)。免疫组织化学结果显示，除BAG外，不仅BAG细胞表达TSLc1，而且BAG细胞以外的其他生长成分的肿瘤细胞也表达TSLC1。这些肿瘤细胞被认为侵袭性较小，因为它们沿着肺泡壁以麻风状生长模式增殖。因此，本研究结果不仅支持TSLC1是NSCLC的肿瘤抑制因子的假说，而且提示TSLC1的完整性可能有助于减少麻风性生长肿瘤细胞的侵袭性表型。
TSLC1 (tumor suppressor in lung cancer-1) is an adhesion molecule of the Ig superfamily that binds homophilically and mediates cell-cell interactions. Originally, TSLC1 was cloned as a candidate tumor suppressor from the genomic region that frequently exhibits loss of heterogeneity in human non-small-cell lung cancer (NSCLC). However, there have been no studies on TSLC1 expression in normal lungs or NSCLC. Here we show that pulmonary epithelial cells express TSLC1 and its expression levels are often decreased or lost in primary pulmonary adenocarcinoma, a major histologic type of NSCLC. Immunohistochemistry revealed that TSLC1 was localized at cell-cell boundaries of all columnar epithelial cells in mouse embryonic lungs of 10.5 and 13 days postcoitus. Similar staining patterns were observed in bronchiolar and alveolar epithelial cells of adult human lungs, suggesting a physiologic role for TSLC1 in interactions of these cells. Next we performed Western blot analyses of TSLC1 in 47 primary pulmonary adenocarcinomas and judged each tumor as either decreased or nondecreased by comparing TSLC1 expression levels of the tumor with the levels of normal lungs. The expression profiles had a significant relation to histologic subtypes but not to other clinicopathologic parameters. Sixteen bronchioloalveolar carcinomas (BACs) were all judged nondecreased, while 19 of 31 (63%) adenocarcinomas other than BAG were judged decreased (p < 0.0001). Immunohistochemistry of tumors judged nondecreased revealed that not only BAG cells but also tumor cells in lepidic growth components of adenocarcinomas other than BAG expressed TSLC1 on their lateral plasma membranes. These tumor cells are considered less invasive because they proliferate in a lepidic growth pattern along alveolar walls. Thus, the present results not only support the hypothesis that TSLC1 is a tumor suppressor of NSCLC but also suggest that preserved integrity of TSLC1 may contribute to less invasive phenotypes of lepidic growth tumor cells.