TREM-1 is induced in tumor associated macrophages by cyclo-oxygenase pathway in human non-small cell lung cancer.
It is increasingly recognized that the tumor microenvironment plays a critical role in the initiation and progression of lung cancer. In particular interaction of cancer cells, macrophages, and inflammatory response in the tumor microenvironment has been shown to facilitate cancer cell invasion and metastasis. The specific molecular pathways in macrophages that immunoedit tumor growth are not well defined. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a member of the super immunoglobulin family expressed on a select group of myeloid cells mainly monocyte/macrophages. Recent studies suggest that expression of TREM-1 in tumors may predict cancer aggressiveness and disease outcomes in liver and lung cancer however the mechanism of TREM-1 expression in the setting of cancer is not defined. In this study we demonstrate that tumor tissue from patients with non-small cell lung cancer show an increased expression of TREM-1 and PGE2. Immunohistochemistry and immunofluorescence confirmed that the expression of TREM-1 was selectively seen in CD68 positive macrophages. By employing an in vitro model we confirmed that expression of TREM-1 is increased in macrophages that are co-cultured with human lung cancer cells. Studies with COX-2 inhibitors and siCOX-2 showed that expression of TREM-1 in macrophages in tumor microenvironment is dependent on COX-2 signaling. These studies for the first time define a link between tumor COX-2 induction, PGE2 production and expression of TREM-1 in macrophages in tumor microenvironment and suggest that TREM-1 might be a novel target for tumor immunomodulation.
Veterans Affairs Medical Center, Gainesville, Florida, United States of America; Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America.
Zhihong
Z
Yuan
Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America.
Hiren J
HJ
Mehta
Veterans Affairs Medical Center, Gainesville, Florida, United States of America; Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America.
Kamal
K
Mohammed
Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America.
Najmunissa
N
Nasreen
Veterans Affairs Medical Center, Gainesville, Florida, United States of America.
Robert
R
Roman
Veterans Affairs Medical Center, Gainesville, Florida, United States of America.
Mark
M
Brantly
Veterans Affairs Medical Center, Gainesville, Florida, United States of America; Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America.
Ruxana T
RT
Sadikot
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015232:Dinoprostone; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone