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Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer

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Pathology & Oncology Research

Abstract

The aim of this study was to study the effects of carbonic anhydrase IX (CA IX) towards the invasion and metastasis of pancreatic cancer. The expressions of CA IX in 58 cases of pancreatic cancer and paired paracancerous normal tissues, obtained from 2005 to 2012 in the first Affiliated Hospital of China Medical University, were detected, as well as its expressions in different pancreatic cancer cell lines, aiming to detect the impacts of CA IX silencing towards the invasion and metastasis of pancreatic cancer cells. The CA IX expressions in 58 pancreatic cancer cases were higher than those in the paired paracancerous normal tissues (P < 0.01), and positively correlated with the tumor size and the UICC staging UICC (P < 0.05), the multivariate analysis showed that the high expression of CA IX was the independent risk factor towards the prognosis of pancreatic cancer (P < 0.05). The CA IX was highly expressed in AxPC–1 and Miapaca–2, and the interference effects were significant. CA IX silencing could significantly inhibit the invasion and metastasis of AxPC-1 and Miapaca. We support a pro-tumor role of CA IX in the development and progression of pancreatic cancer.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60:277–300. doi:10.3322/caac.20073

    Article  PubMed  Google Scholar 

  2. Philip PA, Mooney M, Jaffe D, Eckhardt G, Moore M, Meropol N, Emens L, O’Reilly E, Korc M, Ellis L, Benedetti J, Rothenberg M, Willett C, Tempero M, Lowy A, Abbruzzese J, Simeone D, Hingorani S, Berlin J, Tepper J (2009) Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol 27:5660–5669. doi:10.1200/JCO.2009.21.9022

    Article  PubMed  Google Scholar 

  3. Ivanov S, Liao SY, Ivanova A, Danilkovitch-Miagkova A, Tarasova N, Weirich G, Merrill MJ, Proescholdt MA, Oldfield EH, Lee J, Zavada J, Waheed A, Sly W, Lerman MI, Stanbridge EJ (2001) Expression of hypoxia-induc-ible cell-surface transmembrane carbonic anhydrase in human cancer. Am J Pathol 158:905–919. doi:10.1016/S0002-9440(10)64038-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sundfor K, LyngH REK (1998) Tumour hypoxia and vascular density as predictors of metastasis in squamouscell carcinoma of the uterine cervix. Br J Cancer 78:822–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brizel DM, ScullySP HJM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in humans of tissue sarcoma. Cancer Res 56:941–943

    CAS  PubMed  Google Scholar 

  6. Kim SJ, Rabbani ZN, Dewhirst MW, Vujaskovic Z, Vollmer RT, Schreiber EG, Oosterwijk E, Kelley MJ (2005) Expression of HIF-1, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325–335. doi:10.1016/j.lungcan.2005.03.036

    Article  PubMed  Google Scholar 

  7. Klatte T, Seligson DB, Rao JY, Yu H, de Martino M, Kawaoka K, Wong SG, Belldegrun AS, Pantuck AJ (2009) Carbonic anhydrase IX in bladder cancer: a diagnostic, prognostic, and the rapeutic moleeular marker. Cancer 115:1448–1458. doi:10.1002/cncr.24163

    Article  PubMed  Google Scholar 

  8. Rasheed S, Harris AL, Tekkis PP, Turley H, Silver A, McDonald PJ, Talbot IC, Glynne-Jones R, Northover JM, Guenther T (2009) Assessment of microvessel density and carbonic anhydrase-9 (CA- 9) expression in rectal cancer. Pathol Res Pract 205:1–9. doi:10.1016/j.prp.2008.08.008

    Article  CAS  PubMed  Google Scholar 

  9. Choueiri TK, Regan MM, Rosenberg JE, Oh WK, Clement J, Amato AM, McDermott D, Cho DC, Atkins MB, Signoretti S (2010) Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear- cell renal cell carcinoma receiving vascular endothelia growth factor- targeted therapy. BJU Int 106:772–778. doi:10.1111/j.1464-410X.2010.09218.x

    Article  CAS  PubMed  Google Scholar 

  10. Robertson N, Potter C, Harris AL (2004) Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion. Cancer Res 64:6160–6165. doi:10.1158/0008-5472.CAN-03-2224

    Article  CAS  PubMed  Google Scholar 

  11. Juhász M, Chen J, Lendeckel U, Kellner U, Kasper HU, Tulassay Z, Pastorekova S, Malfertheiner P, Ebert MP (2003) Expression of carbonic anhydrase IX in human pancreatic cancer. Aliment Pharmacol Ther 18:837–846, pii:1738

    Article  PubMed  Google Scholar 

  12. Sheng W, Dong M, Zhou J, Li X, Dong Q (2013) Down regulation of CAII is associated with tumor differentiation and poor prognosis in patients with pancreatic cancer. J Surg Oncol 107:536–543. doi:10.1002/jso.23282

    Article  CAS  PubMed  Google Scholar 

  13. Masunaga R, Kohno H, Dhar DK, Ohno S, Shibakita M, Kinugasa S, Yoshimura H, Tachibana M, Kubota H, Nagasue N (2000) Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res 6:4064–4068

    CAS  PubMed  Google Scholar 

  14. Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172. doi:10.1038/nrclinonc.2009.236

    Article  CAS  PubMed  Google Scholar 

  15. Kivelä AJ, Parkkila S, Saarnio J, Karttunen TJ, Kivelä J, Parkkila AK, Pastoreková S, Pastorek J, Waheed A, Sly WS, Rajaniemi H (2000) Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours. Histochem Cell Biol 114:197–204

    PubMed  Google Scholar 

  16. Kivela AJ, Saarnio J, Karttunen TJ, Kivelä J, Parkkila AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila TS, Rajaniemi H (2001) Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors. Dig Dis Sci 46:2179–2186

    Article  CAS  PubMed  Google Scholar 

  17. Kim SJ, Rabbani ZN, Vollmer RT, Schreiber EG, Oosterwijk E, Dewhirst MW, Vujaskovic Z, Kelley MJ (2004) Carbonic anhydrase IX in early-stage non small cell lung cancer. Clin Cancer Res 10:7925–7933. doi:10.1158/1078-0432.CCR-04-0636

    Article  CAS  PubMed  Google Scholar 

  18. Choschzick M, Oosterwijk E, Müller V, Woelber L, Simon R, Moch H, Tennstedt P (2011) Overexpression of carbonic anhydrase IX (CA IX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer. Virchows Arch 459:193–200. doi:10.1007/s00428-011-1105-y

    Article  CAS  PubMed  Google Scholar 

  19. Schutze D, Milde-Langosch K, Witzel I, Rody A, Karn T, Schmidt M, Choschzick M, Jänicke F, Müller V (2013) Relevance of cellular and serum carbonic anhydrase IX in primary breast cancer. J Cancer Res Clin Oncol 139:747–754. doi:10.1007/s00432-013-1378-4

    Article  PubMed  Google Scholar 

  20. Li MP, Ren LF, Cai HG, Yang HY, Lu B, Zhang P, Bao L (2013) Significance of carbonic anhydrase IX protein expression in molecular subtyping of breast cancers. Zhonghua Bing Li Xue Za Zhi 42:182–185. doi:10.3760/cma.j.issn. 0529-5807.2013.03.009

    CAS  PubMed  Google Scholar 

  21. En-ping BA, Ya-li LV, Lin LIU, Bo ZHAO (2011) Expression of carbonic anhydrase-9 correlates with malignant phenotypes of invasive breast ductal carcinoma. Chin J Clinicians (Electronic Edition) 5:4656–4660. doi:10.3877/cma.j.issn. 1674-0785.2011.16.083

    Google Scholar 

  22. Simi L, Venturini G, Malentacchi F, Gelmini S, Andreani M, Janni A, Pastorekova S, Supuran CT, Pazzagli M, Orlando C (2006) Quantitative analysis of carbonic anhydrase IXmRNA in human non-small cell lung cancer. Lung Cancer 52:59–66. doi:10.1016/j.lungcan.2005.11.017

    Article  PubMed  Google Scholar 

  23. Klimowicz AC, Bose P, Petrillo SK, Magliocco AM, Dort JC, Brockton NT (2013) The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma. Br J Cancer 109:1859–1866. doi:10.1038/bjc.2013.533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim SJ, Shin HJ, Jung KY, Baek SK, Shin BK, Choi J, Kim BS, Shin SW, Kim YH, Kim JS, Oosterwijk E (2007) Prognostic value of carbonic anhydrase IX and Ki-67 exression in squamous cell carcinoma of the tongue. J Clin Onco 37:812–819. doi:10.1093/jjco/hym121

    Google Scholar 

  25. Shin HJ, Rho SB, Jung DC, Han IO, Oh ES, Kim JY (2011) Carbonic anhydrase IX (CA9) modulates tumor-associated cell migration and invasion. J Cell Sci 124:1077–1087. doi:10.1242/jcs.072207

    Article  CAS  PubMed  Google Scholar 

  26. Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman D, Clarke B, Sutherland BW, Waterhouse D, Bally M, Roskelley C, Overall CM, Minchinton A, Pacchiano F, Carta F, Scozzafava A, Touisni N, Winum JY, Supuran CT, Dedhar S (2011) Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res 71:3364–3376. doi:10.1158/0008-5472.CAN-10-4261

    Article  CAS  PubMed  Google Scholar 

  27. De Craene B, Berx G (2013) Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13:97–110. doi:10.1038/nrc3447

    Article  PubMed  Google Scholar 

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All authors have no conflict of interest regarding this paper.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Yuji Li, Ming Dong, Weiwei Sheng & Longping Huang

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  1. Yuji Li
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  2. Ming Dong
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  3. Weiwei Sheng
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  4. Longping Huang
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Correspondence to Ming Dong.

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Li, Y., Dong, M., Sheng, W. et al. Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer. Pathol. Oncol. Res. 22, 277–286 (2016). https://doi.org/10.1007/s12253-015-9935-6

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  • DOI: https://doi.org/10.1007/s12253-015-9935-6

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