Oncotarget

Research Papers:

Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

Melina Schellhorn _, Maria Haustein, Marcus Frank, Michael Linnebacher and Burkhard Hinz

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Oncotarget. 2015; 6:39342-39356. https://doi.org/10.18632/oncotarget.5745

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Abstract

Melina Schellhorn1,*, Maria Haustein1,*, Marcus Frank2, Michael Linnebacher3, Burkhard Hinz1

1Institute of Toxicology and Pharmacology, Rostock University Medical Center, Rostock, Germany

2Electron Microscopy Center, Rostock University Medical Center, Rostock, Germany

3Section of Molecular Oncology and Immunotherapy, Department of General Surgery, Rostock University Medical Center, Rostock, Germany

*These authors have contributed equally to this work

Correspondence to:

Burkhard Hinz, e-mail: burkhard.hinz@med.uni-rostock.de

Keywords: celecoxib, intercellular adhesion molecule 1, lung cancer cells, immune surveillance, lymphokine-activated killer cells

Received: July 06, 2015     Accepted: October 09, 2015     Published: October 22, 2015

ABSTRACT

The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib.


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