Impaired monocyte function in cancer patients: restoration with a cyclooxygenase-2 inhibitor.
Epidemiological data and animal models have provided evidence that nonsteroidal antiinflammatory drugs (NSAIDs) have an anticancer effect. However, the molecular mechanisms underlying these antineoplastic effects are not well understood. We described previously that expression levels of the chemokine receptor, CCR5, and the beta2-integrin, Mac-1, were down-regulated on primary monocytes after incubation in supernatants from human carcinoma cell lines, and that this down-regulation resulted in impaired monocyte function with respect to migration and adhesion. We now demonstrate that these impairments are also present in vivo. Monocytes from cancer patients displayed significantly reduced CCR5 levels and migration capacities in comparison to cells from healthy donors. Because migration is necessary for the antitumor activity of monocytes/macrophages, these deficits may contribute to the suppressed immune system seen in cancer patients. In a clinical study, we analyzed the effect of a selective COX-2 inhibitor, Rofecoxib, on the migration of monocytes derived from cancer patients. The results revealed significant improvement in migration equal to those levels seen in healthy donors. We conclude that in patients with cancer, the intake of Rofecoxib for 3 wk leads to significant restoration of monocyte function. These data may, at least in part, help explain the anticancer effects of NSAIDs.
Lang
Stephan
S
Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Munich D-81377, Germany. stlang@hno.med.uni-muenchen.de
Lauffer
Lina
L
Clausen
Christoph
C
Löhr
Iren
I
Schmitt
Bärbel
B
Hölzel
Dieter
D
Wollenberg
Barbara
B
Gires
Olivier
O
Kastenbauer
Ernst
E
Zeidler
Reinhard
R
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D019713:Receptors, CCR5 / Q000187:drug effects / Q000378:metabolism; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D019713:Receptors, CCR5; D013450:Sulfones; C116926:rofecoxib; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin