Section of General Thoracic Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
J Thorac Cardiovasc Surg. 2012 Feb;143(2):405-11. doi: 10.1016/j.jtcvs.2011.10.026.
Invasive lung tumors are associated with intercellular adhesion molecule-1 (ICAM-1) expression. Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression, and upregulation of PLA(2) activity can enhance metastasis. We hypothesize a link between sPLA(2) activity, ICAM-1 expression, and tumor cell invasion. We propose that inhibition of sPLA(2) modulates ICAM-1 expression in cancer cells and attenuates their invasiveness.
Human lung adenocarcinoma cells (A549) were treated with an ICAM-1 blocking antibody and assayed for invasion. Lung cancer cells (A549 and H358) were then treated with an sPLA(2) inhibitor and evaluated by immunoblotting for ICAM-1 expression. Next cells (A549) treated with sPLA(2) inhibitor were assayed for invasion. Finally, sPLA(2) messenger RNA and protein expression were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence microscopy, respectively. Statistical analysis was performed by the Student t test or analysis of variance, as appropriate.
Antibody blockade of ICAM-1 decreased lung cancer cell invasion. sPLA(2) inhibition significantly reduced ICAM-1 expression and invasion. sPLA(2) inhibition also significantly decreased sPLA(2) mRNA expression and immunofluorescent staining of sPLA(2).
sPLA(2) plays a significant role in mediating the inflammatory signals that induce ICAM-1 expression in lung cancer cells. Inhibition of the enzyme can significantly decrease ICAM-1 expression and subsequent cancer cell invasion. This lays the groundwork for further investigation into the cellular mechanisms of sPLA(2) and its role in lung cancer.
侵袭性肺肿瘤与细胞间黏附分子-1（ICAM-1）的表达有关。分泌型磷脂酶 A2（sPLA2）酶产生的炎症介质可刺激 ICAM-1 的表达，而 PLA2 活性的上调可增强转移。我们假设 sPLA2 活性、ICAM-1 表达与肿瘤细胞侵袭之间存在联系。我们提出抑制 sPLA2 可调节癌细胞中 ICAM-1 的表达并减弱其侵袭性。
用 ICAM-1 阻断抗体处理人肺腺癌细胞（A549）并检测其侵袭性。然后用 sPLA2 抑制剂处理肺癌细胞（A549 和 H358），并通过免疫印迹法检测 ICAM-1 的表达。接着检测 sPLA2 抑制剂处理后的细胞侵袭情况。最后，通过定量逆转录聚合酶链反应和免疫荧光显微镜分别评估 sPLA2 信使 RNA 和蛋白的表达。统计分析采用学生 t 检验或方差分析，视情况而定。
ICAM-1 抗体阻断可降低肺癌细胞的侵袭性。sPLA2 抑制显著降低了 ICAM-1 的表达和侵袭。sPLA2 抑制还显著降低了 sPLA2 mRNA 的表达和 sPLA2 的免疫荧光染色。
sPLA2 在介导诱导肺癌细胞中 ICAM-1 表达的炎症信号中发挥重要作用。抑制该酶可显著降低 ICAM-1 的表达和随后的癌细胞侵袭。这为进一步研究 sPLA2 的细胞机制及其在肺癌中的作用奠定了基础。
