Characterization of morphological alterations in micropapillary adenocarcinoma of the lung using an established cell line
Characterization of morphological alterations in micropapillary adenocarcinoma of the lung using an established cell line
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DOI：
10.3892/or.2021.8230
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发表时间：
2022-01-01
期刊：
影响因子：
4.2
通讯作者：
Satoh, Yukitoshi
中科院分区：
文献类型：
--
作者：
Sonoda, Dai;Kamizaki, Koki;Satoh, Yukitoshi
肺微乳头状腺癌是一种与预后不良相关的癌症，其特征在于存在具有漂浮在肺泡腔内的环状腺结构的肿瘤细胞。在本研究中，其形态学，生化和免疫组化特征，恶性程度之间的关联进行了研究，使用KU-Lu-MPPt 3细胞系从MIP腺癌患者建立。制备KU-Lu-MPPt 3细胞的两个亚群，即粘附（AD）和粘附和悬浮（CS）细胞，并进行DNA微阵列、逆转录定量PCR、western blot和免疫染色分析。使用免疫染色比较细胞类型及其衍生组织之间的蛋白质表达模式。结果显示肺泡腔肿瘤细胞与CS细胞的蛋白表达模式相似，具有MIP腺癌的形态学特征。基于DNA微阵列分析的结果，本研究集中在Akt和粘着斑激酶（FAK），这是显着激活的KU-Lu-MPPt 3 CS和AD细胞，分别。将KU-Lu-MPPt 3 CS细胞接种到胶原包被的培养皿上后，一些细胞在几天内表现出它们的形态向KU-Lu-MPPt 3 AD样细胞的转化，并且它们的Akt和FAK活性与AD细胞的那些相似。此外，用Akt和FAK抑制剂抑制Akt和FAK活性降低KU-Lu-MPPt 3 CS细胞粘附和增殖。因此，上述结果表明FAK和Akt的磷酸化可能分别在KU-Lu-MPPt 3 CS细胞粘附和增殖的调节中起关键作用。此外，MIP腺癌的恶性潜能可能归因于KU-Lu-MPPt 3细胞中的这些形态学和生物化学改变。
Micropapillary adenocarcinoma of the lung is a type of cancer associated with a poor prognosis and is characterized by the presence of tumor cells with a ring-like glandular structure floating within alveolar spaces. In the present study, the association between its morphological, biochemical and immunohistochemical characteristics, and malignancy was investigated using the KU-Lu-MPPt3 cell line established from a patient with MIP adenocarcinoma. Two subpopulations of KU-Lu-MPPt3 cells, namely adhesive (AD) and clumpy and suspended (CS) cells, were prepared and subjected to DNA microarray, reverse transcription-quantitative PCR, western blot and immunostaining analyses. Protein expression patterns were compared between the cell types and their derived tissues using immunostaining. The results revealed similar protein expression patterns between the tumor cells found in the alveolar spaces and CS cells, which exhibited morphological characteristic of MIP adenocarcinoma. Based on the results of DNA microarray analysis, the present study then focused on Akt and focal adhesion kinase (FAK), which were markedly activated in the KU-Lu-MPPt3 CS and AD cells, respectively. Following KU-Lu-MPPt3 CS cell plating onto collagen-coated culture dishes, some cells exhibited a transformation of their morphology into KU-Lu-MPPt3 AD-like cells within a few days, and their Akt and FAK activities were similar to those of the AD cells. Additionally, the inhibition of Akt and FAK activities with Akt and FAK inhibitors reduced KU-Lu-MPPt3 CS cell adhesion and proliferation. Thus, the aforementioned results indicated that the phosphorylation of FAK and Akt may play a crucial role in the regulation of KU-Lu-MPPt3 CS cell adhesion and proliferation, respectively. Furthermore, the malignant potential of MIP adenocarcinoma may be attributed to these morphological and biochemical alterations in the KU-Lu-MPPt3 cells.