Abstract
In this review, we summarize studies that initiated further exploration of the relationship of cyclooxygenase-2 (COX-2) to cancer, and evidence for COX-2 involvement in transformation, maintenance of tumor growth, viability, and metastasis. Included are descriptions of the chronic upregulation of COX-2 in multiple human tumors, as well as the pharmacological evidence of the anti-angiogenic activity of COX-2 inhibitors in animal models. Collectively, these data have generated interest in the functional role of COX-2 during tumorigenesis, and imply COX-2 inhibitors may be effective in the prevention and/or treatment of cancer. Human trials are ongoing to assess the chemopreventive activity of COX-2 inhibitors on progression of premalignant to malignant conditions and/or recurrence. Additionally, COX-2 inhibitors are being tested in combination with standard cytotoxics, radiation, and molecular targeted agents to explore whether combination modalities enhance efficacy of anticancer agents.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res 1999; 59: 4574–4577.
Reeves MJ, Newcomb PA, Trentham-Dietz A, Storer BE, Remington PL. Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. Cancer Epidemiol Biomarkers Prey 1996; 5: 955–960.
Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr. Aspirin use and risk of fatal cancer. Cancer Res 1993; 53: 1322–1327.
Harris RE, Kasbari S, Farrar WB. Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncol Rep 1999; 6: 71–73.
Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 1994; 5: 138–146.
Farrow DC, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prey 1998; 7: 97–102.
Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. Arachidonic acid metabolism. Annu Rev Biochem 1986; 55: 69–102.
Levy GN. Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer. FASEB J 1997; 11: 234–247.
Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta 1996; 1299: 125–140.
Dubois RN, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063–1073.
Murakami M, et al. Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. JBiol Chem 2000; 275:32,783–32,792.
Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108: 15–23.
Simon LS, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998; 41: 1591–1602.
Chan CC, et al. Rofecoxib [Vioxx, MK-0966; 4-(4’-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther 1999; 290: 551–560.
Liu CH, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. JBiol Chem 2001; 276:18,563–18,569.
Reddy BS, et al. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res 2000; 60: 293–297.
Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998; 58: 409–412.
Grubbs CJ, et al. Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res 2000; 60: 5599–5602.
Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999; 20: 1939–1944.
Wilgus TA, Ross MS, Parrett ML, Oberyszyn TM. Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation. Prostaglandins Other Lipid Mediat 2000; 62: 367–384.
Masferrer JL, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 2000; 60: 1306–1311.
Ristimaki A, et al. Expression of cyclooxygenase-2 in human transitional cell carcinoma of the urinary bladder. Am J Pathol 2001; 158: 849–853.
Okajima E, et al. Chemopreventive effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on the development of rat urinary bladder carcinomas initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine. Cancer Res 1998; 58: 3028–3031.
Hida T, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 1998; 58: 3761–3764.
Kulkarni S, et al. Cyclooxygenase-2 is overexpressed in human cervical cancer. Clin Cancer Res 2001; 7: 429–434.
Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ. Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 2001; 8: 97–114.
Koki AT, Leahy KM, Masferrer JL. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opinion on Investigational Drugs 1999; 8 (10): 1623–1638.
Giardiello FM, et al. Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis. Dig Dis Sci 1998; 43: 311–316.
Giardiello FM, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993; 328: 1313–1316.
Labayle D, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 1991; 101: 635–639.
Singh AK, Trotman BW. Use and safety of aspirin in the chemoprevention of colorectal cancer. JAssoc Acad Minor Phys 1998; 9: 40–44.
Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–1899.
Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Ann Intern Med 1991; 115: 787–796.
MacDonald TM, et al. Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study. Br Med J 1997; 315: 1333–1337.
Henry D, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from non-aspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 1993; 105: 1078–1088.
Agrawal NM. Epidemiology and prevention of non-steroidal anti-inflammatory drug effects in the gastrointestinal tract. Br J Rheumatol 1995; 34 (Suppl 1): 5–10.
Roth SH. A controlled clinical investigation of 3% diclofenac/2.5% sodium hyaluronate topical gel in the treatment of uncontrolled pain in chronic oral NSAID users with osteoarthritis. Int J Tissue React 1995; 17: 129–132.
Cheatum DE, Arvanitakis C, Gumpel M, Stead H, Geis GS. An endoscopie study of gastroduodenal lesions induced by nonsteroidal anti-inflammatory drugs. Clin Ther 1999; 21: 992–1003.
Silverstein FE, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284: 1247–1255.
Langman MJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999; 282: 1929–1933.
Steinbach G, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000; 342: 1946–1952.
Shirahama T, Sakakura C. Overexpression of cyclooxygenase-2 in squamous cell carcinoma of the urinary bladder. Clin Cancer Res 2001; 7: 558–561.
Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancer in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. JNCI 2001; 92: 1500–1510.
Hemminki K, Dong C, Frisch M. Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. Eur J Cancer Prey 2001; 9: 433–437.
Koga H, et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Hepatology 1999; 29: 688–696.
Rahman MA, et al. Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C viruspositive cases. Clin Cancer Res 2001; 7: 1325–1332.
Murata H, et al. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol 1999; 94: 451–455.
Fu S, et al. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 1999; 116: 1319–1329.
Chariyalertsak S, et al. Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma. Gut 2001; 48: 80–86.
Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res 1998; 58: 2929–2934.
Chan G, et al. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 1999; 59: 991–994.
Ambs S, et al. Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. Cancer Res 1998; 58: 334–341.
Marrogi AJ, et al. Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma. Clin Cancer Res 2000; 6: 4739–4744.
Ryu HS, et al. High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion. Gynecol Oncol 2000; 76: 320–325.
Buckman SY, et al. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 1998; 19: 723–729.
Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997; 57: 1276–1280.
Lim HY, et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 2000; 6: 519–525.
Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G. Cyclooxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: ex vivo induction by bile salts and acid exposure. Gastroenterology 2000; 118: 487–496.
Dohadwala M, et al. Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. J Biol Chem 2001; 276:20,809–20,812.
Gupta RA, Dubois RN. Translational studies on Cox-2 inhibitors in the prevention and treatment of colon cancer. Ann NYAcad Sci 2000; 910: 196–204.
Yoshimura R, et al. Expression of cyclooxygenase-2 in prostate carcinoma. Cancer 2000; 89: 589–596.
Knapp DW, et al. Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 1994; 8: 273–278.
Mohammed SI, et al. Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999; 59: 5647–5650.
Moon RC, et al. Chemoprevention of OH-BBN-induced bladder cancer in mice by piroxicam. Carcinogenesis 1993; 14: 1487–1489.
Tucker ON, et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 1999; 59: 987–990.
Yip-Schneider MT, et al. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis 2000; 21: 139–146.
Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 1999; 59: 4356–4362.
Cordon-Cardo C, et al. Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma. J Natl Cancer Inst 1998; 90: 1284–1291.
Shiotani H, et al. Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-l-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res 2001; 61: 1451–1456.
Souza RF, Shewmake K, Beer DG, Cryer B, Specifier SJ. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res 2000; 60: 5767–5772.
Pasricha PJ, et al. The effects of sulindac on colorectal proliferation and apoptosis in familial adenoma-tous polyposis. Gastroenterology 1995; 109: 994–998.
Verheul HM, Panigrahy D, Yuan J, D’Amato RJ. Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits. Br J Cancer 1999; 79: 114–118.
Bosch-Marce M, et al. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology 1999; 116: 1167–1175.
Sung JJ, et al. Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol 2000; 157: 729–735.
Sawaoka H, et al. Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa. Prostaglandins Leukot Essent Fatty Acids 1998; 59: 313–316.
Ezra DB. Neovasculogenesis. Triggering factors and possible mechanisms. Sury Ophthalmol 1979; 24: 167–176.
Bouck N, Stellmach V, Hsu SC. How tumors become angiogenic. Adv Cancer Res 1996; 69: 135–174.
Akhtar M, et al. Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res 2001; 61: 2399–2403.
Toyota M, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 1999; 59: 5438–5442.
Giovannucci E. The prevention of colorectal cancer by aspirin use. Biomed Pharmacother 1999; 53: 303–308.
Smalley WE, Dubois RN. Colorectal cancer and nonsteroidal anti-inflammatory drugs. Adv Pharmacol 1997; 39: 1–20.
Levin G, Kariv N, Khomiak E, Raz A. Indomethacin inhibits the accumulation of tumor cells in mouse lungs and subsequent growth of lung metastases. Chemotherapy 2000; 46: 429–437.
Oshima M, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87: 803–809.
Khuri FR, et al. Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 2001; 7: 861–867.
Wardlaw SA, March TH, Belinsky SA. Cyclooxygenase-2 expression is abundant in alveolar type II cells in lung cancer-sensitive mouse strains and in premalignant lesions. Carcinogenesis 2000; 21: 1371–1377.
Achiwa H, et al. Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas. Clin Cancer Res 1999; 5: 1001–1005.
Harris RE, Alshafie GA, Abou-Isla H, Seibert K. Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Cancer Res 2000; 60: 2101–2103.
Paganini-Hill A, Chao A, Ross RK, Henderson BE. Aspirin use and chronic diseases: a cohort study of the elderly. Br Med J 1989; 299: 1247–1250.
Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA. Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 1996; 88: 988–993.
Sharpe CR, et al. Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer 2000; 83: 112–120.
Howe LR, Subbaramaiah K, Chung WJ, Dannenberg AJ, Brown AM. Transcriptional activation of cyclooxygenase-2 in Wnt- 1-transformed mouse mammary epithelial cells. Cancer Res 1999; 59: 1572–1577.
Howe LR, et al. PEAS is up-regulated in response to Wntl and activates the expression of cyclooxygenase-2. J Biol Chem 2001; 276:20,108–20,115.
Jin Z, et al. Adenomatous polyposis coli (APC) gene promoter hypermethylation in primary breast cancers. Br J Cancer 2001; 85: 69–73.
Zhao Y, Agarwal VR, Mendelson CR, Simpson ER. Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 1996; 137: 5739–5742.
Brueggemeier RW, et al. Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 1999; 140: 27–35.
Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Increased expression of cyclooxygenase-2 in HER-2 over-expressing human breast cancer cells. NCI 7th Spore Invesigator’ Workshop. 1999b.
Sumitani K, et al. 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 2001; 30: 41–47.
Erickson BA, Longo WE, Panesar N, Mazuski JE, Kaminski DL. The effect of selective cyclooxygenase inhibitors on intestinal epithelial cell mitogenesis. J Surg Res 1999; 81: 101–107.
Nolan RD, Danilowicz RM, Eling TE. Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. Mol Pharmacol 1988; 33: 650–656.
Goin M, Pignataro O, Jimenez DA. Early cell cycle diacylglycerol (DAG) content and protein kinase C (PKC) activity enhancement potentiates prostaglandin F2 alpha (PGF2 alpha) induced mitogenesis in Swiss 3T3 cells. FEBS Lett 1993; 316: 68–72.
Bandyopadhyay GK, Imagawa W, Wallace D, Nandi S. Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor. J Biol Chem 1987; 262: 2750–2756.
Longo WE, et al. The effect of phospholipase A2 inhibitors on proliferation and apoptosis of murine intestinal cells. J Surg Res 1999; 84: 51–56.
Sawaoka H, et al. Effects of NSAIDs on proliferation of gastric cancer cells in vitro: possible implication of cyclooxygenase-2 in cancer development. J Clin Gastroenterol 1998; 27 (Suppl 1): S47 - S52.
Fosslien E. Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 2000; 30: 3–21.
Liu XH, et al. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000; 164: 820–825.
Tsujii M, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells [published erratum appears in Cell 1998 Jul 24;94(2):following 271]. Cell 1998; 93: 705–716.
Hsu AL, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bc1–2. J Biol Chem 2000; 275:11,397–11,403.
Tanji N, Kikugawa T, Yokoyama M. Immunohistochemical study of cyclooxygenases in prostatic adenocarcinoma; relationship to apoptosis and Bc1–2 protein expression. Anticancer Res 2000; 20: 2313–2319.
Leahy KM, Koki AT, Masferrer JL. Role of cyclooxygenases in Angiogenesis. Curr Med Chem 2000; 7: 1163–1170.
Majima M, et al. Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants. BrJPharmacol 2000; 130: 641–649.
Yamada M, Kawai M, Kawai Y, Mashima Y. The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat. Curr Eye Res 1999; 19: 300–304.
Gallo O, et al. Cyclooxygenase-2 pathway correlates with vegf expression in head and neck cancer. implications for tumor angiogenesis and metastasis. Neoplasia 2001; 3: 53–61.
Kage K, et al. Basic fibroblast growth factor induces cyclooxygenase-2 expression in endothelial cells derived from bone. Biochem Biophys Res Commun 1999; 254: 259–263.
Sasaki E, et al. Induction of cyclooxygenase-2 in a rat gastric epithelial cell line by epiregulin and basic fibroblast growth factor. J Clin Gastroenterol 1998: 27 (Suppl 1): S21 - S27.
Goddard DH, Grossman SL, Newton R, Clark MA, Bomalaski JS. Regulation of synovial cell growth: basic fibroblast growth factor synergizes with interleukin 1 beta stimulating phospholipase A2 enzyme activity, phospholipase A2 activating protein production and release of prostaglandin E2 by rheumatoid arthritis synovial cells in culture. Cytokine 1992; 4: 377–384.
Vasile E, Qu H, Dvorak HF, Dvorak AM. Caveolae and vesiculo-vacuolar organelles in bovine capillary endothelial cells cultured with VPFNEGF on floating Matrigel-collagen gels. JHistochem Cytochem 1999; 47: 159–167.
Chiarugi V, Magnelli L, Gallo O. Cox-2, iNOS and p53 as play-makers of tumor angiogenesis (review). Int J Mol Med 1998; 2: 715–719.
Feng D, et al. Pathways of macromolecular extravasation across microvascular endothelium in response to VPFNEGF and other vasoactive mediators. Microcirculation 1999; 6: 23–44.
Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 1999; 56: 794–814.
Li S, et al. Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy. Int J Cancer 2001; 91: 789–796.
Fukumura D, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998; 94: 715–725.
Williams CS, Tsujii M, Reese J, Dey SK, Dubois RN. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 2000; 105: 1589–1594.
Ziche M, Jones J, Gullino PM. Role of prostaglandin El and copper in angiogenesis. J Natl Cancer Inst 1982; 69: 475–482.
Form DM, Auerbach R. PGE2 and angiogenesis. Proc Soc Exp Biol Med 1983; 172: 214–218.
Cheng T, Cao W, Wen R, Steinberg RH, LaVail MM. Prostaglandin E2 induces vascular endothelial growth factor and basic fibroblast growth factor mRNA expression in cultured rat Muller cells. Invest Ophthalmol Vis Sci 1998; 39: 581–591.
Ben Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 1995; 372: 83–87.
Bamba H, Ota S, Kato A, Kawamoto C, Fujiwara K. Prostaglandins up-regulate vascular endothelial growth factor production through distinct pathways in differentiated U937 cells. Biochem Biophys Res Commun 2000; 273: 485–491.
Skold M, et al. Induction of VEGF and VEGF receptors in the spinal cord after mechanical spinal injury and prostaglandin administration [In Process Citation]. Eur J Neurosci 2000; 12: 3675–3686.
Nie D, et al. Thromboxane A(2) regulation of endothelial cell migration, angiogenesis, and tumor metastasis. Biochem Biophys Res Commun 2000; 267: 245–251.
Wheeler-Jones C, et al. Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. FEBS Lett 1997; 420: 28–32.
He H, et al. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. JBiol Chem 1999; 274:25,130–25,135.
Gliki G, Abu-Ghazaleh R, Jezequel S, Wheeler-Jones C, Zachary I. Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-delta and by mobilization of intracellular Ca2+. Biochem J 2001; 353: 503–512.
Moncada S. Eighth Gaddum Memorial Lecture. University of London Institute of Education, December 1980. Biological importance of prostacyclin. Br J Pharmacol 1982; 76: 3–31.
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997; 18: 4–25.
Murohara T, et al. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation 1998; 97: 99–107.
Fujii E, et al. Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Naunyn Schmiedebergs Arch Pharmacol 1997; 356: 475–480.
Collins PD, Connolly DT, Williams TJ Characterization of the increase in vascular permeability induced by vascular permeability factor in vivo. Br J Pharmacol 1993; 109: 195–199.
Hernandez GL, et al. Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 2001; 193: 607–620.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Koki, A.T., Leahy, K.M., Harmon, J.M., Masferrer, J.L. (2003). Cyclooxygenase-2 and Cancer. In: Harris, R.E. (eds) COX-2 Blockade in Cancer Prevention and Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-302-6_12
Download citation
DOI: https://doi.org/10.1007/978-1-59259-302-6_12
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-304-6
Online ISBN: 978-1-59259-302-6
eBook Packages: Springer Book Archive