Department of Thoracic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0374, Japan.
Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650‑0017, Japan.
Oncol Rep. 2022 Jan;47(1). doi: 10.3892/or.2021.8230. Epub 2021 Nov 19.
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.
肺微乳头状腺癌是一种预后不良的癌症,其特征是肿瘤细胞呈环状腺样结构漂浮在肺泡腔内。本研究通过建立于肺微乳头状腺癌患者的 KU-Lu-MPPt3 细胞系,研究了其形态、生化和免疫组织化学特征与恶性程度的关系。制备了 KU-Lu-MPPt3 细胞的两个亚群,即黏附(AD)和成团悬浮(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。采用免疫染色比较了细胞类型及其衍生组织之间的蛋白表达模式。结果表明,肺泡腔中发现的肿瘤细胞与 CS 细胞具有相似的蛋白表达模式,CS 细胞表现出肺微乳头状腺癌的形态特征。基于 DNA 微阵列分析的结果,本研究进一步关注 Akt 和粘着斑激酶(FAK),它们在 KU-Lu-MPPt3 CS 和 AD 细胞中分别显著激活。KU-Lu-MPPt3 CS 细胞接种于涂有胶原蛋白的培养皿后,数天内部分细胞的形态发生转化,成为类似 KU-Lu-MPPt3 AD 的细胞,其 Akt 和 FAK 活性与 AD 细胞相似。此外,Akt 和 FAK 抑制剂抑制 Akt 和 FAK 活性可降低 KU-Lu-MPPt3 CS 细胞的黏附和增殖。因此,上述结果表明,FAK 和 Akt 的磷酸化可能分别在调节 KU-Lu-MPPt3 CS 细胞黏附和增殖中发挥关键作用。此外,MIP 腺癌的恶性潜能可能归因于 KU-Lu-MPPt3 细胞的这些形态和生化改变。