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Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Review

Cyclooxygeanse-2 promotes metastasis in osteosarcoma

Authors: Liyan Qu, Bing Liu

Published in: Cancer Cell International | Issue 1/2015

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Abstract

Cyclooxygenase-2 (COX-2), an inducible form of the enzyme that catalyzes the first step in the synthesis of prostanoids, is associated with carcinogenesis, which is suspected to promote angiogenesis and tissue invasion of tumors and resistance to apoptosis. COX-2 is also involved in metastasis and poor prognosis of cancer. Osteosarcoma with COX-2 positivity is from 67 to 92 %. COX-2-positive rate in metastatic lesions was greater than that of biopsy and/or resected samples of the primary site in osteosarcoma. And, what role does COX-2 play in osteosarcoma metastasis? Genetic studies support a cause-effect connection between COX-2 and tumorigenesis. COX-2 expression had a poor prognosis with regard to metastasis, and patients with increased COX-2 expression in lung metastases died of the disease. COX-2 expression has also been established as a marker in human osteosarcoma, and COX-2 inhibition has been suggested as a possible way of improving therapeutic outcome. In addition, COX-inhibitors inhibit the tumor initiation, matrix metalloproteinases (MMPs), cell differentiation and T cell proliferation and suppression of the antitumor activity of natural killer cells and macrophages, angiogenic mechanism. Therefore, we can exert the COX-inhibitors to potentialize the effects of chemotherapeutic agents, and reverse the metastasis in osteosarcoma to facilitate the patient who may benefit from addition of COX-inhibitors to standard cytotoxic therapy.
Literature
1.
go back to reference Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107:1183–8.PubMed Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107:1183–8.PubMed
2.
go back to reference Koga H, Sakisaka S, Ohishi M, Kawaguchi T, Taniguchi E, Sasatomi K, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology. 1999;29:688–96.PubMedCrossRef Koga H, Sakisaka S, Ohishi M, Kawaguchi T, Taniguchi E, Sasatomi K, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology. 1999;29:688–96.PubMedCrossRef
3.
go back to reference Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 1999;59:987–90.PubMed Tucker ON, Dannenberg AJ, Yang EK, Zhang F, Teng L, Daly JM, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 1999;59:987–90.PubMed
4.
go back to reference Hwang D, Scollard D, Byrne J, Levine E. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst. 1998;90:445–60.CrossRef Hwang D, Scollard D, Byrne J, Levine E. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst. 1998;90:445–60.CrossRef
5.
go back to reference Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 1998;58:3761–4.PubMed Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 1998;58:3761–4.PubMed
6.
go back to reference Naruse T, Nishida Y, Hosono K, Ishiguro N. Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis. 2006;27:584–92.PubMedCrossRef Naruse T, Nishida Y, Hosono K, Ishiguro N. Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis. 2006;27:584–92.PubMedCrossRef
7.
go back to reference Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997;94:3336–40.PubMedCentralPubMedCrossRef Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997;94:3336–40.PubMedCentralPubMedCrossRef
8.
go back to reference Urakawa H, Nishida Y, Naruse T, Nakashima H, Ishiguro N. Cyclooxygenase-2 overexpression predicts poor survival in patients with high-grade extremity osteosarcoma: a pilot study. Clin Orthop Relat Res. 2009;467:2932–8.PubMedCentralPubMedCrossRef Urakawa H, Nishida Y, Naruse T, Nakashima H, Ishiguro N. Cyclooxygenase-2 overexpression predicts poor survival in patients with high-grade extremity osteosarcoma: a pilot study. Clin Orthop Relat Res. 2009;467:2932–8.PubMedCentralPubMedCrossRef
9.
go back to reference Rodriguez NI, Hoots WK, Koshkina NV, Morales-Arias JA, Arndt CA, Inwards CY, et al. COX-2 expression correlates with survival in patients with osteosarcoma lung metastases. J Pediatr Hematol Oncol. 2008;30:507–12.PubMedCentralPubMedCrossRef Rodriguez NI, Hoots WK, Koshkina NV, Morales-Arias JA, Arndt CA, Inwards CY, et al. COX-2 expression correlates with survival in patients with osteosarcoma lung metastases. J Pediatr Hematol Oncol. 2008;30:507–12.PubMedCentralPubMedCrossRef
10.
go back to reference Tsujii M, DuBois RN. Alterations in cellular adhesions and apoptosis in epithelial cells overexpressing prostaglandin endoperoxidase synthase 2. Cell. 1995;83:493–501.PubMedCrossRef Tsujii M, DuBois RN. Alterations in cellular adhesions and apoptosis in epithelial cells overexpressing prostaglandin endoperoxidase synthase 2. Cell. 1995;83:493–501.PubMedCrossRef
11.
go back to reference Nzeako UC, Guicciardi ME, Yoon JH, Bronk SF, Gores GJ. COX-2 inhibits Fas-mediate apoptosis in cholangiocarcinoma cells. Hepatology. 2002;35:552–9.PubMedCrossRef Nzeako UC, Guicciardi ME, Yoon JH, Bronk SF, Gores GJ. COX-2 inhibits Fas-mediate apoptosis in cholangiocarcinoma cells. Hepatology. 2002;35:552–9.PubMedCrossRef
12.
go back to reference Dickens DS, Kozielski R, Leavey PJ, Timmons C, Cripe TP. Cyclooxygenase-2 expression does not correlate with outcome in osteosarcoma or rhabdomyosarcoma. J Pediatr Hematol Oncol. 2003;25:282–5.PubMedCrossRef Dickens DS, Kozielski R, Leavey PJ, Timmons C, Cripe TP. Cyclooxygenase-2 expression does not correlate with outcome in osteosarcoma or rhabdomyosarcoma. J Pediatr Hematol Oncol. 2003;25:282–5.PubMedCrossRef
13.
go back to reference Masi L, Recenti R, Silvestri S, Pinzani P, Pepi M, Paglierani M, et al. Expression of cyclooxygenase-2 in osteosarcoma of bone. Appl Immunohistochem Mol Morphol. 2007;15:70–6.PubMedCrossRef Masi L, Recenti R, Silvestri S, Pinzani P, Pepi M, Paglierani M, et al. Expression of cyclooxygenase-2 in osteosarcoma of bone. Appl Immunohistochem Mol Morphol. 2007;15:70–6.PubMedCrossRef
14.
go back to reference Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci. 2002;99:13926–31.PubMedCentralPubMedCrossRef Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci. 2002;99:13926–31.PubMedCentralPubMedCrossRef
15.
go back to reference Tsujii M, Kawano S, Tsuji S, Saeaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–16.PubMedCrossRef Tsujii M, Kawano S, Tsuji S, Saeaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–16.PubMedCrossRef
16.
go back to reference PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.PubMedCentralPubMedCrossRef PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.PubMedCentralPubMedCrossRef
17.
go back to reference Krishnan K, Khanna C, Helman LJ. The biology of metastases in pediatric sarcomas. Cancer J. 2005;11:306–13.PubMedCrossRef Krishnan K, Khanna C, Helman LJ. The biology of metastases in pediatric sarcomas. Cancer J. 2005;11:306–13.PubMedCrossRef
19.
go back to reference Kashima T, Nakamura K, Kawaguchi J, Takanashi M, Ishida T, Aburatani H, et al. Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo. Int J Cancer. 2003;104:147–54.PubMedCrossRef Kashima T, Nakamura K, Kawaguchi J, Takanashi M, Ishida T, Aburatani H, et al. Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo. Int J Cancer. 2003;104:147–54.PubMedCrossRef
20.
go back to reference Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904.PubMedCrossRef Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904.PubMedCrossRef
21.
go back to reference Worth LL, Lafleur EA, Jia SF, Kleinerman ES. Fas expression inversely correlates with metastatic potential in osteosarcoma cells. Oncol Rep. 2002;9:823–7.PubMed Worth LL, Lafleur EA, Jia SF, Kleinerman ES. Fas expression inversely correlates with metastatic potential in osteosarcoma cells. Oncol Rep. 2002;9:823–7.PubMed
22.
go back to reference Levings PP, McGarry SV, Currie TP, Nickerson DM, McClellan S, Ghivizzani SC, et al. Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res. 2009;69:5648–55.PubMedCentralPubMedCrossRef Levings PP, McGarry SV, Currie TP, Nickerson DM, McClellan S, Ghivizzani SC, et al. Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res. 2009;69:5648–55.PubMedCentralPubMedCrossRef
23.
go back to reference Saini V, Hose CD, Monks A, Nagashima K, Han B, Newton DL, et al. Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma. PLoS One. 2012;7, e41401.PubMedCentralPubMedCrossRef Saini V, Hose CD, Monks A, Nagashima K, Han B, Newton DL, et al. Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma. PLoS One. 2012;7, e41401.PubMedCentralPubMedCrossRef
24.
go back to reference Pang LY, Gatenby EL, Kamida A, Whitelaw BA, Hupp TR, Argyle DJ. Global Gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation. PLoS One. 2014;9, e83144.PubMedCentralPubMedCrossRef Pang LY, Gatenby EL, Kamida A, Whitelaw BA, Hupp TR, Argyle DJ. Global Gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation. PLoS One. 2014;9, e83144.PubMedCentralPubMedCrossRef
25.
go back to reference Klein G, Vellenga E, Fraaije MW, Kamps WA, de Bont ESJM. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol. 2004;50:87–100.PubMedCrossRef Klein G, Vellenga E, Fraaije MW, Kamps WA, de Bont ESJM. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol. 2004;50:87–100.PubMedCrossRef
26.
go back to reference Lee EJ, Choi EM, Kim SR, Park JH, Kim H, Ha KS, et al. Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells. Exp Mol Med. 2007;39:469–76.PubMedCrossRef Lee EJ, Choi EM, Kim SR, Park JH, Kim H, Ha KS, et al. Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells. Exp Mol Med. 2007;39:469–76.PubMedCrossRef
27.
go back to reference Liu B, Shi ZL, Feng J, Tao HM. Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int. 2008;32:494–501.PubMedCrossRef Liu B, Shi ZL, Feng J, Tao HM. Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int. 2008;32:494–501.PubMedCrossRef
28.
29.
go back to reference Bergin E, Levine JS, Koh JS, Lieberthal W. Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism. Am J Physiol. 2000;278:758–68. Bergin E, Levine JS, Koh JS, Lieberthal W. Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism. Am J Physiol. 2000;278:758–68.
30.
go back to reference Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell. 1999;98:147–57.PubMedCrossRef Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell. 1999;98:147–57.PubMedCrossRef
31.
go back to reference Tran NL, Adams DG, Vaillancourt RR, Heimark RL. Signal transduction from N-cadherin increases Bcl-2. Regulation of the phosphatidylinositol 3-kinase/Akt pathway by homophilic adhesion and actin cytoskeletal organization. J Biol Chem. 2002;277:32905–14.PubMedCrossRef Tran NL, Adams DG, Vaillancourt RR, Heimark RL. Signal transduction from N-cadherin increases Bcl-2. Regulation of the phosphatidylinositol 3-kinase/Akt pathway by homophilic adhesion and actin cytoskeletal organization. J Biol Chem. 2002;277:32905–14.PubMedCrossRef
32.
go back to reference Cook D, Fry MJ, Hughes K, Sumathipala R, Woodgett JR, Dale TC. Wingless inactivates glycogen synthase kinase-3 via an intracellular signaling pathway which involves a protein kinase C. EMBO J. 1996;15:4526–36.PubMedCentralPubMed Cook D, Fry MJ, Hughes K, Sumathipala R, Woodgett JR, Dale TC. Wingless inactivates glycogen synthase kinase-3 via an intracellular signaling pathway which involves a protein kinase C. EMBO J. 1996;15:4526–36.PubMedCentralPubMed
33.
go back to reference Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11:3286–305.PubMedCrossRef Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11:3286–305.PubMedCrossRef
34.
go back to reference Klein R, Nanduri V, Jing SA, Lamballe F, Tapley P, Bryant S, et al. The trkB tyrosine protein kinase is a receptor for brainderived neurotrophic factor and neurotrophin-3. Cell. 1991;66:395–403.PubMedCentralPubMedCrossRef Klein R, Nanduri V, Jing SA, Lamballe F, Tapley P, Bryant S, et al. The trkB tyrosine protein kinase is a receptor for brainderived neurotrophic factor and neurotrophin-3. Cell. 1991;66:395–403.PubMedCentralPubMedCrossRef
35.
go back to reference Douma S, van Laar T, Zevenhoven J, Meuwissen R, van Garderen E, Peeper DS. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430:1034–9.PubMedCrossRef Douma S, van Laar T, Zevenhoven J, Meuwissen R, van Garderen E, Peeper DS. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430:1034–9.PubMedCrossRef
36.
go back to reference Asanuma H, Torigoe T, Kamiguchi K, Hirohashi Y, Ohmura T, Hirata K, et al. Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-Kinase/AKT signaling pathway in breast cancer cells. Cancer Res. 2005;65:11018–25.PubMedCrossRef Asanuma H, Torigoe T, Kamiguchi K, Hirohashi Y, Ohmura T, Hirata K, et al. Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-Kinase/AKT signaling pathway in breast cancer cells. Cancer Res. 2005;65:11018–25.PubMedCrossRef
37.
go back to reference Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, et al. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J Clin Invest. 2003;111:727–35.PubMedCentralPubMedCrossRef Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, et al. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J Clin Invest. 2003;111:727–35.PubMedCentralPubMedCrossRef
38.
go back to reference Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res. 2002;62(3):625–31.PubMed Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res. 2002;62(3):625–31.PubMed
40.
go back to reference Liekens S, De Clercq E, Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol. 2001;61:253–70.PubMedCrossRef Liekens S, De Clercq E, Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol. 2001;61:253–70.PubMedCrossRef
41.
go back to reference Bellamy WT, Richter L, Sirjani D, Roxas C, Glinsmann-Gibson B, Frutiger Y. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood. 2001;97:1427–34.PubMedCrossRef Bellamy WT, Richter L, Sirjani D, Roxas C, Glinsmann-Gibson B, Frutiger Y. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood. 2001;97:1427–34.PubMedCrossRef
42.
go back to reference Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol. 1997;17:4015–23.PubMedCentralPubMed Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol. 1997;17:4015–23.PubMedCentralPubMed
43.
go back to reference Zhao Q, Wang C, Zhu J, Wang L, Dong S, Zhang G, et al. RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study. J Exp Clin Cancer Res. 2011;30:26.PubMedCentralPubMedCrossRef Zhao Q, Wang C, Zhu J, Wang L, Dong S, Zhang G, et al. RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study. J Exp Clin Cancer Res. 2011;30:26.PubMedCentralPubMedCrossRef
Metadata
Title
Cyclooxygeanse-2 promotes metastasis in osteosarcoma
Authors
Liyan Qu
Bing Liu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0220-2

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