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Open Access 01-06-2009 | Research Paper

Inhibition of cyclooxygenase-2 suppresses the invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 production and activation

Authors: Yuji Kurihara, Masashi Hatori, Yuriko Ando, Daisuke Ito, Takahiko Toyoshima, Makoto Tanaka, Satoru Shintani

Published in: Clinical & Experimental Metastasis | Issue 5/2009

Abstract

Increased cyclooxygenase (COX-2) expression in tumors is known to be correlated with tumor invasion, angiogenesis, resistance to apoptosis, and suppression of host immunity. We previously reported that the invasiveness of human oral squamous cell carcinoma (OSCC) cell lines NA and HSC-4 was suppressed by treatment with either NS-398, a selective COX-2 inhibitor, or COX-2 antisense oligonucleotide (AS). In the present study, to explore the effects of COX-2 inhibition on the interaction between cancer cells and fibroblasts, we examined the effects of these anti-COX-2 reagents on the expression of matrix metalloproteinases (MMPs) in fibroblast cell lines WI-38 and MRC-5. Western blotting and enzyme-linked immunosorbent assay revealed that NS-398 and COX-2 AS down-regulated the expression and secretion of MMP-2 and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human fibroblast cell lines. Furthermore, invasion activity of OSCC cells was down-regulated by the addition of culture supernatant from fibroblasts treated with anti-COX-2 reagents in a Matrigel^® invasion assay. These results suggest that selective COX-2 inhibition suppresses the invasion activity of OSCC cells via down-regulation of an MMP-2-activating mechanism involving TIMP-2 and production of the MMP-2 protein by an interaction between cancer cells and stromal fibroblasts. Genetic or pharmacological inhibition of COX-2 may therefore be a beneficial strategy in the treatment of OSCC.

Eberhart CE, Dubois RN (1995) Eicosanoids and the gastrointestinal tract. Gastroenterology 109(1):285–301. doi:10.1016/0016-5085(95)90296-1 PubMedCrossRef

Marnett LJ (1992) Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res 52(20):5575–5589PubMed

Hosoi T, Takeda K, Konno K (1989) Synergism of prostaglandin E2 plus TNF in induction of differentiation of human monocytoid leukemic U-937 cells. Anticancer Res 9(3):615–618PubMed

Herschman HR (1996) Prostaglandin synthase 2. Biochim Biophys Acta 1299(1):125–140PubMed

Dubois RN, Abramson SB, Crofford L et al (1998) Cyclooxygenase in biology and disease. FASEB J 12(12):1063–1073PubMed

Williams CS, Smalley W, Dubois RN (1997) Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Investig 100(6):1325–1329. doi:10.1172/JCI119651 PubMedCrossRef

Gupta S, Srivastava M, Ahmad N et al (2000) Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 42(1):73–78. doi:10.1002/(SICI)1097-0045(20000101)42:1<73::AID-PROS9>3.0.CO;2-G PubMedCrossRef

Wolff H, Saukkonen K, Anttila S et al (1998) Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58(22):4997–5001PubMed

Zimmermann KC, Sarbia M, Weber AA et al (1999) Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 59(1):198–204PubMed

10.

Tucker ON, Dannenberg AJ, Yang EK et al (1999) Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 59(5):987–990PubMed

11.

Chan G, Boyle JO, Yang EK et al (1999) Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 59(5):991–994PubMed

12.

Masferrer JL, Leahy KM, Koki AT et al (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60(5):1306–1311PubMed

13.

Uefuji K, Ichikura T, Mochizuki H (2000) Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res 6(1):135–138PubMed

14.

Sato H, Takino T, Okada Y et al (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61–65. doi:10.1038/370061a0 PubMedCrossRef

15.

Sumitani K, Kamijo R, Toyoshima T et al (2001) Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production. J Oral Pathol Med 30(1):41–47. doi:10.1034/j.1600-0714.2001.300107.x PubMedCrossRef

16.

Kinugasa Y, Hatori M et al (2004) Inhibition of cyclooxygenase-2 suppresses invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 and CD44. Clin Exp Metastasis 21:737–745. doi:10.1007/s10585-005-1190-x PubMedCrossRef

17.

Tang DW, Lin SC, Chang KW et al (2003) Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma–evidence for COX-2 induction by areca quid ingredients in oral keratinocytes. J Oral Pathol Med 32(9):522–529. doi:10.1034/j.1600-0714.2003.00182.x PubMedCrossRef

18.

Tang X, Sun YJ, Half E et al (2002) Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers resistance to tumor necrosis factor related apoptosis-inducing ligand-induced apoptosis in human colon cancer cells. Cancer Res 62(17):4903–4908PubMed

19.

Leung WK, To KF, Go MY et al (2003) Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. Int J Oncol 23(5):1317–1322PubMed

20.

Huang M, Stolona M, Sharma S et al (1998) Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 58(6):1208–1216PubMed

21.

Abiru S, Nakao K, Ichikawa T et al (2002) Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells. Hepatology (Baltimore) 35(5):1117–1124. doi:10.1053/jhep.2002.32676

22.

Tisty TD (2001) Stromal cells can contribute oncogenic signals. Semin Cancer Biol 11:97–104. doi:10.1006/scbi.2000.0361 CrossRef

23.

Radisky D, Hagios C, Bissell MJ (2001) Tumors are unique organs defined by abnormal signaling and context. Semin Cancer Biol 11:87–95. doi:10.1006/scbi.2000.0360 PubMedCrossRef

24.

Che AM, Jung TH, Choi JH et al (2006) Collagen-based co-culture for invasive study on cancer cells–fibroblasts interaction. Biochem Biophys Res Commun 346:268–275. doi:10.1016/j.bbrc.2006.05.111 PubMedCrossRef

25.

Sympson CJ, Werb Z, Bissell MJ (1995) Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1. Semin Cancer Biol 6:159–163. doi:10.1006/scbi.1995.0022 PubMedCrossRef

26.

Sternlicht MD, Lochter A, Sympson CJ et al (1999) The stromal proteinase MMP3/Stromelysin-1 promotes mammary carcinogenesis. Cell 98:137–146. doi:10.1016/S0092-8674(00)81009-0 PubMedCrossRef

27.

Hofmann UB, Westphal JR, Zendman AJ et al (2000) Expression and activation of matrix metalloproteinase-2 (MMP-2) and its co-localization with membrane-type matrix metalloproteinase 1 (MT1-MMP) correlate with melanoma progression. J Pathol 191:245–256. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH632>3.0.CO;2-# PubMedCrossRef

28.

Hofmann UB, Eggert AAO, Blass K et al (2003) Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 63(23):8221–8225PubMed

29.

Westermarck J, Kähäri V-M (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792PubMed

30.

Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89(17):1260–1270. doi:10.1093/jnci/89.17.1260 PubMedCrossRef

31.

Yang C, Zeisberg M, Lively JC et al (2003) Integrin alpha1beta1 and alpha2beta1 are the key regulators of hepatocarcinoma cell invasion across the fibrotic matrix microenvironment. Cancer Res 63(23):8312–8317PubMed

32.

Robinson CM, Stone AM, Shields JD et al (2003) Functional significance of MMP-2 and MMP-9 expression by human malignant oral keratinocyte cell lines. Arch Oral Biol 48(11):779–786. doi:10.1016/S0003-9969(03)00172-9 PubMedCrossRef

33.

Bernardo MM, Fridman R (2003) TIMP-2 (tissue inhibitor of metalloproteinase-2) regulates MMP-2 (matrix metalloproteinase-2) activity in the extracellular environment after pro-MMP-2 activation by MT1 (membrane type 1)-MMP. Biochem J 374:739–745. doi:10.1042/BJ20030557 PubMedCrossRef

34.

Attiga FA, Fernandez PM, Weeraratna AT et al (2000) Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. Cancer Res 60(16):4629–4637PubMed

35.

Sato T, n Ovejero M, Hou P et al (1997) Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts. J Cell Sci 110(5):589–596PubMed

36.

Hiraoka N, Allen E, Apel IJ et al (1998) Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95(3):365–377. doi:10.1016/S0092-8674(00)81768-7 PubMedCrossRef

37.

Seiki M, Yana I (2003) Roles of pericellular proteolysis by membrane type-1 matrix metalloproteinase in cancer invasion and angiogenesis. Cancer Sci 94(7):569–574. doi:10.1111/j.1349-7006.2003.tb01484.x PubMedCrossRef

38.

Seiki M (2003) Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett 194(1):1–11. doi:10.1016/S0304-3835(02)00699-7 PubMedCrossRef

39.

Knauper V, Will H, Lopez-Otin C et al (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase (MMP-2) are able to generate active enzyme. J Biochem 271(29):17124–17131

40.

Brew K, Kinakarpandian K, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure, and function. Biochim Biophys Acta 1477:267–283PubMed

41.

Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9:541–573. doi:10.1146/annurev.cb.09.110193.002545 PubMedCrossRef

42.

Sato T, Iwai M, Sakai T et al (1999) Enhancement of membrane-type 1-matrix metalloproteinase (MT1-MMP) production and sequential activation of progelatinase A on human squamous carcinoma cells co-cultured with human dermal fibroblasts. Br J Cancer 80:1137–1143. doi:10.1038/sj.bjc.6690477 PubMedCrossRef

43.

Noël A, Hajitou A, L’Hoir C et al (1998) Inhibition of stromal matrix metalloproteinases: effects on breast-tumor promotion by fibroblasts. Int J Cancer 76:267–273. doi:10.1002/(SICI)1097-0215(19980413)76:2<267::AID-IJC15>3.0.CO;2-9 PubMedCrossRef

44.

Kruger A, Sanchez-Sweatman OH, Martin DC et al (1998) Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line. Oncogene 16:2419–2423. doi:10.1038/sj.onc.1201774 PubMedCrossRef

45.

Wang M, Liu YE, Greene S et al (1997) Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4. Oncogene 14:2767–2774. doi:10.1038/sj.onc.1201245 PubMedCrossRef

46.

Baker AH, George SJ, Zaltsman AB, Murphy G, Newby AC (1999) Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3. Br J Cancer 79:1347–1355. doi:10.1038/sj.bjc.6690217 PubMedCrossRef

47.

Basset P, Bellocq JP, Wolf C et al (1990) A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348:699–704. doi:10.1038/348699a0 PubMedCrossRef

48.

Sorsa T, Tjaderhane L, Salo T (2004) Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 10:311–318. doi:10.1111/j.1601-0825.2004.01038.x PubMedCrossRef

49.

Okada A, Bellocq JP, Rouyer N et al (1995) Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92:2730–2734. doi:10.1073/pnas.92.7.2730 PubMedCrossRef

Title: Inhibition of cyclooxygenase-2 suppresses the invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 production and activation
Authors: Yuji Kurihara
Masashi Hatori
Yuriko Ando
Daisuke Ito
Takahiko Toyoshima
Makoto Tanaka
Satoru Shintani
Publication date: 01-06-2009
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 5/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-009-9241-3

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