Estrogen Activates Cyclooxygenase-2 and CD44 Expressions and Promotes Cholangiocarcinoma Cell Invasion
Keywords:
Cholangiocarcinoma, Invasion, Estrogen, Cyclooxygenase-2, NS398Abstract
Cholangiocarcinoma (CCA)is one of the worst prognosis cancers. CCA usually presents in advanced stage according to its high metastatic property. Until present, the factors involving in CCA metastasis are still unclear. Estrogen has been revealed as a stimulator of the invasiveness of CCA. Cyclooxygenase-2 (COX-2), an estrogen targeted gene, associates with cancer invasion and metastasis. This study aims to investigate the role of COX-2 in estrogen-stimulated invasion of CCA cells. KKU-100 and KKU-M213 CCA cell lines were treated with 17β-estradiol (E2), as active form of estrogen, and NS398, a selective COX-2 inhibitor, and the invasive property of cancer cells was measured as well as the expression levels of some metastatic genes. The results indicated that E2 could stimulate CCA cell invasion and this process was inhibited by NS398. In addition, in E2-stimulated CCA cells, the levels of COX-2 and CD44 were increased. These results indicate the impact of COX-2-mediated CD44 expression in E2-driven CCA invasion. The application of using COX-2 inhibitor to attenuate E2-stimulated invasion of CCA is of great interest to propose in the effective management of the disease.
References
Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS (1986) Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci U S A 83: 2496–2500.
Brandi G, Venturi M, Pantaleo MA, Ercolani G; GICO (2016) Cholangiocarcinoma: Current opinion on clinical practice diagnostic and therapeutic algorithms: A review of the literature and a long-standing experience of a referral center. Dig Liver Dis 48: 231–241.
Cervello M, Montalto G (2006) Cyclooxygenases in hepatocellular carcinoma. World J Gastroenterol 12: 5113–5121.
Esbona K, Inman D, Saha S, Jeffery J, Schedin P, Wilke L, Keely P (2016) COX-2 modulates mammary tumor progression in response to collagen density. Breast Cancer Res 18: 35.
Esnaola NF, Meyer JE, Karachristos A, Maranki JL, Camp ER, Denlinger CS (2016) Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma. Cancer 122: 1349–1369.
Ghosh N, Chaki R, Mandal V, Mandal SC (2010) COX-2 as a target for cancer chemotherapy. Pharmacol Rep 62: 233–244.
Half E, Arber N (2009) Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin Pharmacother 10: 211–219.
Han C, Leng J, Demetris AJ, Wu T (2004) Cyclooxygenase-2 promotes human cholangiocarcinoma growth: evidence for cyclooxygenase-2-independent mechanism in celecoxib-mediated induction of p21waf1/cip1 and p27kip1 and cell cycle arrest. Cancer Res 64: 1369–1376.
Harris RE (2009) Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 17: 55–67.
Ho CC, Ling YC, Chang LW, Tsai HT, Tsai MH, Lin P (2008) 17-Beta estradiol and hydroxyestradiols interact via the NF-kappa B pathway to elevate cyclooxygenase 2 expression and prostaglandin E2 secretion in human bronchial epithelial cells. Toxicol Sci 104: 294–302.
Huang RY, Chen GG (2011) Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta 1815: 158–169.
Hunsawong T, Singsuksawat E, In-chon N, Chawengrattanachot W, Thuwajit C, Sripa B, Paupairoj A, Chau-in S, Thuwajit P (2012) Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro. J Cancer Res Clin Oncol 138: 1311–1320.
Itatsu K, Sasaki M, Yamaguchi J, Ohira S, Ishikawa A, Ikeda H, Sato Y, Harada K, Zen Y, Sato H, et al. (2009) Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha. Am J Pathol 174: 829–841.
Kabbach G, Assi HA, Bolotin G, Schuster M, Lee HJ, Tadros M (2015) Hepatobiliary Tumors: Update on Diagnosis and Management. J Clin Transl Hepatol 3:169–181.
Kinugasa Y, Hatori M, Ito H, Kurihara Y, Ito D, Nagumo M (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.
Kunlabut K, Vaeteewoottacharn K, Wongkham C, Khuntikeo N, Waraasawapati S, Pairojkul C, Wongkham S (2012) Aberrant expression of CD44 in bile duct cancer correlates with poor prognosis. Asian Pac J Cancer Prev 13 Suppl: 95–99.
Laborda J (1991) 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucleic Acids Res 19: 3998.
Li M, Kuo L, Stallone JN (2008) Estrogen potentiates constrictor prostanoid function in female rat aorta by upregulation of cyclooxygenase-2 and thromboxane pathway expression. Am J Physiol Heart Circ Physiol 294: H2444–H2455.
Miwa M, Honjo S, You G, Tanaka M, Uchida K, Srivatanakul P, Khuhaprema T, Loilome W, Techasen A, Wongkham C, et al. (2014) Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand. World J Gastrointest Pathophysiol 5: 570–578.
Narasaka T, Moriya T, Endoh M, Suzuki T, Shizawa S, Mizokami Y, Matsuoka T, Sasano H (2000) 17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver. Endocr J 47: 697–705.
Pandey V, Wu ZS, Zhang M, Li R, Zhang J, Zhu T, Lobie PE (2014) Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma. Breast Cancer Res 16: 429.
Patrono C (2016) Cardiovascular Effects of Cyclooxygenase-2 Inhibitors: A Mechanistic and Clinical Perspective. Br J Clin Pharmacol [Epub ahead of print].
Pongcharoen P, Jinawath A, Tohtong R (2011) Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells. Clin Exp Metastasis 28: 827–839.
Pruthi RS, Wallen EM (2005) Cyclooxygenase-2: a therapeutic target for prostate cancer. Clin Genitourin Cancer 4: 203–211.
Rodrigues S, Nguyen QD, Faivre S, Bruyneel E, Thim L, Westley B, May F, Flatau G, Mareel M, Gespach C, et al. (2001) Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase- and thromboxane A2 receptor-dependent signaling pathways. FASEB J 15:1517–1528.
Sahin M, Sahin E, Gümüslü S (2009) Cyclooxygenase-2 in cancer and angiogenesis. Angiology 60: 242–253.
Salehifar E, Hosseinimehr SJ (2016) The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today 21: 654–662.
Samir R, Tot T, Asplund A, Pekar G, Hellberg D (2010) Increased serum progesterone and estradiol correlate to increased COX-2 tissue expression in cervical intraepithelial neoplasia. Anticancer Res 30: 1217–1222.
Sripa B, Leungwattanawanit S, Nitta T, Wongkham C, Bhudhisawasdi V, Puapairoj A, Sripa C, Miwa M (2005) Establishment and characterization of an opisthorchiasis-associated cholangiocarcinoma cell line (KKU-100). World J Gastroenterol 11: 3392–3397.
Thapa R, Wilson GD (2016) The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer. Stem Cells Int 2016: 2087204.
Thuwajit P, Chawengrattanachot W, Thuwajit C, Sripa B, May FE, Westley BR, Tepsiri NN, Paupairoj A, Chau-In S (2007) Increased TFF1 trefoil protein expression in Opisthorchis viverrini-associated cholangiocarcinoma is important for invasive promotion. Hepatol Res 37: 295–304.
Tübel J, Kuntz L, Marthen C, Schmitt A, Wiest I, VON Eisenhart-Rothe R, Jeschke U, Burgkart R (2016) Methylation of the ER-alpha Promoter Is Influenced by its Ligand Estrogen in Osteosarcoma Cells SAOS-2 In Vitro. Anticancer Res 36: 3199–3204.
Tuncer S, Banerjee S (2015) Eicosanoid pathway in colorectal cancer: Recent updates. World J Gastroenterol 21: 11748–11766.
Watkins JF, Mayo MS, Smith HJ, Williamson SK (2009) Gemcitabine, irinotecan and celecoxib in patients with biliary cancer. Anticancer Drugs 20: 294–300.
Wu T (2005) Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma. Biochim Biophys Acta 1755: 135–150.
Yoon JH, Canbay AE, Werneburg NW, Lee SP, Gores GJ (2004) Oxysterols induce cyclooxygenase-2 expression in cholangiocytes: implications for biliary tract carcinogenesis. Hepatology 39: 732–738.
