Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A 2 inhibition

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Abstract

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. © 2012 by The American Association for Thoracic Surgery.

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Yu, J. A., Sadaria, M. R., Meng, X., Mitra, S., Ao, L., Fullerton, D. A., & Weyant, M. J. (2012). Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A 2 inhibition. Journal of Thoracic and Cardiovascular Surgery, 143(2), 405–411. https://doi.org/10.1016/j.jtcvs.2011.10.026

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