Polymorphonuclear cells stimulate the migration and metastatic potential of rat sarcoma cells

Abstract

The tumour microenvironment, which is largely composed of inflammatory cells, is a crucial participant in the neoplastic process through the promotion of cell proliferation, survival and migration. Neutrophil polymorphonuclear cells (PMNs) induce inflammatory reactions that can be either cytotoxic for tumour cells or can promote tumour growth and metastasis. Previously, we have reported a spontaneous metastasis tumour model that has tumour PMNs infiltration, and metastasis, to liver and spleen. The aim of this study was to evaluate the PMNs influences on the tumour cell invasion and metastatic properties. We analysed intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator receptor (uPAR), MT1-MMP (membrane type 1-matrix metalloproteinase) and MMP2 protein expression in TuE-t cells cultured with PMNs or PMNs-conditioned medium isolated from tumour bearing and normal rats. The interaction between tumour cells and PMNs induced a decrease in ICAM-1 expression in tumour cells as well as an increase in MMP2 and tumour cell motility. Besides, conserved expression of uPAR and MT1-MMP in tumour cells was also demonstrated. The up-regulation in MMP2 associated with uPAR and MT1-MMP conserved expression may be related to an increased extracellular matrix proteolysis. These results showed that the interaction of tumour cells with PMNs could favour tumour cell spreading through the promotion of a tumour invasive phenotype.

Combined Detection of Preoperative Neutrophil-to-Lymphocyte Ratio and CEA as an Independent Prognostic Factor in Nonmetastatic Patients Undergoing Colorectal Cancer Resection Is Superior to NLR or CEA Alone

“…Patients with elevated NLR showed a relative lymphopenia and a high-circulating neutrophil level [ 25 ]. Neutrophils are known to play a key role in all stages of tumor progression by (1) producing a number of ligands and secretion of matrix metalloproteinases (MMPs), thus inducing tumor cell proliferation and invasion [ 26 ]; (2) releasing proangiogenic chemokines and other cytokines to promote tumor vascular formation [ 27 , 28 ]; and (3) interacting with T cell, thus affecting tumor cell proliferation, angiogenesis, and metastasis [ 29 ]. Taken together, neutrophils may act as a tumor-promoting factor in various stages of cancer [ 30 ].…”

Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma

“…Mast cells may be effective in inducing neutrophil migration to inflammatory sites [54] , numerous transmigrated neutrophils were observed in the larynx tumor samples. Despite their known function as phagocytes, the role of tumor-associated neutrophils in neoplastic progression has been controversial [19] , [55] . Neutrophils can induce DNA damage in proliferating cells through the generation of reactive oxygen and nitrogen species, which are normally produced by these cells to fight infection [55] .…”

“…Although there is evidence suggesting a role for neutrophils in enhanced disease progression in specific human tumors, the relationship between neutrophil infiltration and prognosis in human cancer has not been systematically investigated [18] . The role of neutrophils in tumor progression remains controversial [19] largely because these cells have both tumor-promoting and tumoricidal functions depending on the presence of transforming growth factor beta (TGF-β) [20] , [21] .…”

Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate

“…In addition, ENA-78 was reported to be an attractant for neutrophils [ 48 ], which can also be involved in tumour growth and metastasis [ 49 ].…”