Distinct Pattern of Inflammatory Enzyme Activities in Human Ovarian Cancer and Benign Myoma
Keywords:NAG (N-acetylglucosaminidase), MPO (Myeloperoxidase), Neutrophils, Macrophages, Enzymes, inflammatory response, Ovarian cancer, inflammation, myoma, pelvic surgery
Objective: Inflammatory cells and their products are significant components of malignancies. This study was performed to determine the activity of inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in ascitic fluid, sera or peritoneal lavage fluid from patients with epithelial ovarian cancer (EOC). Methods: Eighteen patients age ranging from 25 to 79 years (54.6±2.9 years) with epithelial ovarian cancer submitted to surgical treatment (EOC group) and 17 patients with uterine myoma (Myoma group) submitted to abdominal hysterectomy (control group) were prospectively studied. MPO and NAG activities were evaluated colorimetrically in sera, ascites or peritoneal lavage fluid obtained from the patients at the time of laparotomy. Results: In a total of 18 EOC, there were stage I in 1 case (5.5%), II in 3 (16.7%), III in 11 (61.1%) and IV in 3 cases (16.7%). MPO activity in sera of EOC was higher than in the ascitic fluid from the same patients. Conversely, MPO activity was similar in sera from both EOC and myoma-bearing patients. Comparison between NAG activities in sera from both groups showed much higher values in the OEC patients. Furthermore, inflammatory enzyme activities were overall associated with the stage of the disease. Conclusions: Our results show that inflammation has been positively correlated with cancer and that the pattern of a systemic inflammatory response induced by EOC differs quantitatively from that of a typical benign pelvic condition. The most important limitation lies in the fact that the number of patients and controls was relatively small. Further studies with a larger number of patients and longer follow-up are necessary to assess the accuracy of the diagnostic and prognostic impact of these results.
Look K. Epidemiology, etiology, and screening of ovarian cancer. In: Rubin SC, Sutton GP, Eds., Ovarian cancer (2nd ed.), Lippincott Williams & Wilkins, Philadelphia, Pennsylvania 2001; pp. 167-80.
Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. Int J Gynaecol Obstet 2003; 83(Suppl 1): 135-66. http://dx.doi.org/10.1016/S0020-7292(03)90118-4
Cannistra SA. Cancer of ovary. N Engl J Med 1993; 329 (21): 1550-559. http://dx.doi.org/10.1056/NEJM199311183292108
Ohshima H, Bartsch H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res 1994; 305: 253-64. http://dx.doi.org/10.1016/0027-5107(94)90245-3
Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role of inflammatory disease and progression to cancer. Biochem J 1996; 313: 17-29.
Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357: 539-45. http://dx.doi.org/10.1016/S0140-6736(00)04046-0
Coussens LM, Werb Z. Inflammatory cells and cancer: think different! J Exp Med 2001; 19; 193(6): 727-40.
Lewis EC, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006; 66(2): 605-612. http://dx.doi.org/10.1158/0008-5472.CAN-05-4005
Negus RP, Stamp GM, Hadley J, Balkwill FR. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 1997; 150(5): 1723-34.
Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001; 193: 727: 40.
Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Bio 2005; 77: 598-25. http://dx.doi.org/10.1189/jlb.1204697
Trush MA, Seed JL, Kensler TW. Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer. Proc Natl Acad Sci USA 1985; 82(15): 5194-8. http://dx.doi.org/10.1073/pnas.82.15.5194
Van Rensburg CEJ, Van Staden AM, Anderson R, Van Rensburg EJ, Hypochlorous acid potentiates hydrogen peroxide-mediated DNA-strand breaks in human mononuclear leucocytes. Mutat Res 1992; 265: 255-61. http://dx.doi.org/10.1016/0027-5107(92)90054-6
Woynarowska B, Wikiel H, Bernacki RJ. Human ovarian carcinoma -N-acethylglucosaminidase isoenzymes and their role in extracellular matrix degradation. Cancer Res 1989; 49: 5598-604.
Gil Martin E, Gil-Seijo S, Nieto-Novoa C, Fernandez-Briera A. Elevation of acid glycosidase activities in thyroid and gastric tumors. Int J Biochem Cell Biol 1996; 28(6): 651-57. http://dx.doi.org/10.1016/1357-2725(96)00010-6
Belo AV, Barcelos LS, Teixeira MM, Ferreira MAND, Andrade SP. Differential effects of antiangiogenic compounds in neovascularization, leukocyte recruitment, VEGF production, and tumor growth in mice. Cancer Invest 2004; 22: 723-29. http://dx.doi.org/10.1081/CNV-200032992
Severini G, Aliberti M. Serum N-acetyl-beta-glucosaminidase activity in breast cancer. Cancer Biochem Biophys 1994; 14: 87-92.
Luqmani Y, Temmim L, Memon A, et al. Measurement of serumN-acetyl glucosaminidase activity in patients with breast cancer. Acta Oncol 1999; 38: 649-53. http://dx.doi.org/10.1080/028418699431267
Song M, Santanam M. Increased myeloperoxidase and lipid peroxidise-modified protein in gynaecological malignancies. Antioxid Redox Signal 2001; 3(6): 1139-46. http://dx.doi.org/10.1089/152308601317203648
Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78(3): 206-9. http://dx.doi.org/10.1111/1523-1747.ep12506462
Baley PJ. Sponge implants as models. Methods Enzymol 1988; 162: 327-34. http://dx.doi.org/10.1016/0076-6879(88)62087-8
Freedman RS, Deavers M, Liu J, Wang E. Peritoneal inflammation-A microenvironment for epithelial ovarian cancer (EOC). J Transl Med 2004; 2: 1-10. http://dx.doi.org/10.1186/1479-5876-2-23
Wang X, Deavers M, Patenia R, et al. Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med 2006; 6(4): 30.
Olsson I, Olofsson T, Ohlsson K, Gustavsson A. Serum and plasma myeloperoxidase, elastase and lactoferrin content in acute myeloid leukaemia. Scand J Haematol 1979; 22(5): 397-06. http://dx.doi.org/10.1111/j.1600-0609.1979.tb00437.x
Dobrossy L, Pavelic Z, Vaughan M, Porter N, Bernacki RJ. Elevation of lysosomal enzymes in primary lung tumor correlated with the initiation of metastasis. Cancer Res 1980; 40: 3281-85.
Robinson-Smith TM, Isaacsohn I, Mercer CA, et al. Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res 2007; 67: 5708-16. http://dx.doi.org/10.1158/0008-5472.CAN-06-4375