+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Radiation-induced matrix metalloproteinases limit natural killer cell-mediated anticancer immunity in NCI-H23 lung cancer cells

Radiation-induced matrix metalloproteinases limit natural killer cell-mediated anticancer immunity in NCI-H23 lung cancer cells

Molecular Medicine Reports 11(3): 1800-1806

Radiotherapy has been used to treat cancer for >100 years and is required by numerous patients with cancer. Ionizing radiation effectively inhibits the growth of cancer cells by inducing cell death and increasing anticancer immunity, through the induction of natural killer group 2 member D ligands (NKG2DLs); however, adverse effects have also been reported, including the promotion of metastasis. Matrix metalloproteinases (MMPs) are induced by ionizing radiation and have an important role in the invasion and metastasis of cancer cells. Previously, MMPs were demonstrated to increase the shedding of NKG2DLs, which may reduce the surface expression of NKG2DLs on cancer cells. As a consequence, the cancer cells may escape natural killer (NK)‑mediated anticancer immunity. In the present study, NCI‑H23 human non‑small cell lung cancer cells were used to investigate the combined effects of ionizing radiation and MMP inhibitors on the expression levels of NKG2DLs. Ionizing radiation increased the expression of MMP2 and ADAM metalloproteinase domain 10 protease, as well as NKG2DLs. The combined treatment of ionizing radiation and MMP inhibitors increased the surface expression levels of NKG2DLs and resulted in the increased susceptibility of the cancer cells to NK‑92 natural killer cells. Furthermore, soluble NKG2DLs were increased in the media by ionizing radiation and blocked by MMP inhibitors. The present study suggests that radiotherapy may result in the shedding of soluble NKG2DLs, through the induction of MMP2, and combined treatment with MMP inhibitors may minimize the adverse effects of radiotherapy.

(PDF emailed within 0-6 h: $19.90)

Accession: 055345250

Download citation: RISBibTeXText

PMID: 25385045

DOI: 10.3892/mmr.2014.2918

Related references

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. International Journal of Oncology 48(2): 843-853, 2016

Anti-tumor immunity induced by Interleukin-12 gene therapy in a metastatic model of breast cancer is mediated by natural killer cells. Breast Cancer Research & Treatment 60(2): 129-134, 2000

Spontaneous fits after febrile convulsions induced by cytomegalovirus infection role of specific cell mediated immunity and natural killer cells. Journal of Neuroimmunology (SUPPL 1): S27, 1982

Investigating the lysis of small-cell lung cancer cell lines by activated natural killer (NK) cells with a fluorometric assay for NK-cell-mediated cytotoxicity. Cancer Immunology Immunotherapy 48(4): 209-213, 1999

Influence of natural killer cells and perforin‑mediated cytolysis on the development of chemically induced lung cancer in A/J mice. Cancer Immunology, ImmunoTherapy 63(6): 571-580, 2014

Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity induced by Chrysanthemum coronarium L. International Immunopharmacology 11(2): 226-232, 2011

Studies on the mechanism of natural killer cell mediated cyto toxicity 1. release of cyto toxic factors specific for natural killer sensitive target cells during co culture of natural killer effector cells with natural killer target cells. Journal of Immunology 129(1): 433-439, 1982

Matrix metalloproteinases produced by IL-2 activated natural killer cells and extracellular matrix degradation. Natural Immunity 15(4): 187, 1996-, 1997

Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model. Clinical and Experimental Immunology 159(1): 93-99, 2010

Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in non-small-cell lung cancer. Invasion & Metastasis 18(3): 134-141, 1999

Sensitivity to acetyl tyrosine ethyl ester inhibition of cell mediated killing distinguishes freshly isolated natural killer cells from both in vitro activated natural killer cells and t killer cells. Federation Proceedings 41(3): ABSTRACT 851, 1982

The antiangiogenic action of cisplatin on endothelial cells is mediated through the release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells. Oncotarget 9(75): 34038-34055, 2018

CD1D-mediated stimulation of natural killer T cells selectively activates hepatic natural killer cells in interferon-gamma independent manner and induces the activation of acquired immunity against murine hepatocellular carcinoma. Hepatology 38(4 Suppl 1): 771A, 2003

Expression of matrix metalloproteinases 3, 10 and 11 (stromelysins 1, 2 and 3) and matrix metalloproteinase 7 (matrilysin) by cancer cells in non-small cell lung neoplasms. Clinicopathologic studies. Ceskoslovenska Patologie 42(1): 16-19, 2006

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs. Experimental and Therapeutic Medicine 10(4): 1437-1444, 2015