Combined IL-8 and TGF-beta blockade efficiently prevents neutrophil infiltrates into an A549-cell tumor.
Neutrophil infiltrates into tumors have been reported in certain circumstances to reduce tumor growth and in other circumstances to augment tumor growth, particularly by facilitating metastasis. Neutrophil chemotaxis can be facilitated by both interleukin-8 (IL-8) and transforming growth factor-beta (TGF-beta). However, the combined effects of these two cytokines on neutrophil tumor infiltrates is unknown, and we considered the possibility that studying the combined effects might resolve apparent contradictions with regard to neutrophil effects on tumor development. First, we determined that a simultaneous IL-8 and TGF-beta blockade is far more efficient at eliminating the neutrophil infiltrate from an A549 derived tumor than is blockade of either cytokine alone. Blockade of IL-8 alone, led to smaller tumors, consistent with the known inhibitory role of TGF-beta on A549 cell proliferation. Blockade of TGF-beta alone rescued the tumor growth but led to reduced metastasis volume. Surprisingly, blockade of both cytokines rescued both tumor volume and metastasis, underscoring the difficulty of understanding the effects of complete tumor cytokine elaboration profiles by isolating the effects of only one cytokine.
Kazemfar
Kristy
K
Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, United States.
Chen
Ren
R
Nicholson
Kimberly
K
Coppola
Domenico
D
Zhou
Jun-Min
JM
Chen
Xianghong
X
Wei
Sheng
S
Blanck
George
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D016212:Transforming Growth Factor beta