DOI QR코드

DOI QR Code

The Feasibility of Cathepsin B Level in Preoperatively Screening Patients with Thyroid Cancer and Nodular Hyperplasia

갑상선암 및 결절성 증식증 환자의 수술전 스크리닝을 위한 cathepsin B의 발현 양상

  • Choi, Young-Sik (Department of Internal medicine, Kosin University College of Medicine) ;
  • Kim, Young-Ok (Department of Pathology, Kosin University College of Medicine) ;
  • Kim, Woo-Mi (Department of Pharmacology, Kosin University College of Medicine)
  • 최영식 (고신대학교 의과대학 내과학교실) ;
  • 김영옥 (고신대학교 의과대학 병리학교실) ;
  • 김우미 (고신대학교 의과대학 약리학교실)
  • Published : 2009.11.30

Abstract

To evaluate the feasibility of cathepsin-B levels in preoperatively screening patients with thyroid cancer, we assigned these patients to either the thyroid cancer group (n=32) or the nodular hyperplasia group (n=7). Five healthy volunteers served as controls (n=5). We quantified cathepsin-B expressions in cancerous lesions with follicular carcinoma and hyperplastic lesions with nodular hyperplasia, and compared the degrees to those of normal thyroid tissue, which was obtained from matched contralateral lobe. The activity of serum cathepsin B was significantly higher in patients with thyroid carcinoma ($284.87{\pm}79.32$, ${\times}10^{-2}\;mU$) and those with nodular hyperplasia ($255.45{\pm}95.68$, ${\times}10^{-2}\;mU$) than compared to normal control ($168.94{\pm}15.10$, ${\times}10^{-2}\;mU$) (p<0.05). Based on the results of immunoassay, the concentrations of cathepsin B in the thyroid cancer group ($15.50{\pm}7.86\;ng/ml$) and the nodular hyperplasia group ($17.64{\pm}7.49\;ng/ml$) were higher than those of the control group ($4.85{\pm}0.61\;ng/ml$). The degree of cathepsin-B mRNA expression was significantly higher in cancerous or hyperplastic lesions than normal thyroid tissues from matched contralateral lobe with follicular carcinoma or non-neoplastic thyroid disease. Our results indicate that the activity of serum cathepsin B is a useful indicator in screening patients with nodular hyperplasia or neoplastic thyroid disease and it may be involved in the abnormal proliferation of cells.

혈장 cathepsin B 활성도 측정이 갑상선암 및 결절성 증식증의 수술 전 진단에 도움이 되는지를 알아보고자 분화갑상선암 32례, 결절성 증식증 7례, 대조군 5례의 혈장 cathepsin B 발현양상을 대조군과 함께 관찰하였다. 수술시 제거된 여포선암의 암조직, 결절성 증식증 조직의 cathepsin B 발현을 정상 조직과 비교하였다. 혈장 Cathepsin B 활성도는 정상 대조군에서 $168.94{\pm}15.10$ (${\times}10^{-2}$, mU), 결절성 증식증에서 $255.45{\pm}95.68$ (${\times}10^{-2}$, mU), 악성종양에서 $284.87{\pm}79.32$ (${\times}10^{-2}$, mU)로써 악성종양군과 결절성 증식증군에서 cathepsin B 발현이 정상 대조군보다 비교적 높게 나타났다(p<0.05). 혈장 cathepsin B의 정량적 비교를 위한 immunoassay결과에서도 결절성 증식증군($17.64{\pm}7.49\;ng/ml$)과 악성종양군($15.50{\pm}7.86\;ng/ml$)에서 정상대조군($4.85{\pm}0.61\;ng/ml$)보다 높은 수치를 나타내었다(p<0.05). 결절성 증식증 및 악성종양군의 조직 내 cathepsin B mRNA발현이 정상 조직에서보다 높게 나타났다. 따라서 혈장 cathepsin B는 갑상선세포의 비정상적인 증식시에 증가됨을 알 수 있으며, 갑상선암 혹은 결절성 증식증을 스크리닝하는데 이용될 수 있을 것으로 사료된다.

Keywords

References

  1. Aznavoorian, S. and A. N. Wurphy.1993. Molecular aspects of tumor cell invasion and metastasis. Cancer 71, 1368-1383 https://doi.org/10.1002/1097-0142(19930215)71:4<1368::AID-CNCR2820710432>3.0.CO;2-L
  2. Chabowski, A., M. Sulkowska, S. Sulkowski, W. Famulski, E. Skrzydlewska, and W. Kisielewski. 2001. Immunohistochemical evaluation of cathepsin D expression in colorectal cancer. Histochem. Cytobiol. 39, 153-154
  3. Coussens, L. M., B. Fingleton, and L. M. Matrisian. 2002. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387-2392 https://doi.org/10.1126/science.1067100
  4. Curran, S. and G. I. Murray. 1999. Matrix metalloproteinases in tumour invasion and metastasis. J. Pathol. 189, 300-308 https://doi.org/10.1002/(SICI)1096-9896(199911)189:3<300::AID-PATH456>3.0.CO;2-C
  5. Foekens, J. A., M. P. Look, Bolt-de, J. Vries, Meijer-van, M. E. Gelder, van, W. L. Putten, and J. G. Klijn. 1999. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br. J. Cancer 79, 300-307 https://doi.org/10.1038/sj.bjc.6690048
  6. Gocheva, V., W. Zeng, D. Ke, D. Klimstra, T. Reinheckel, C. Peters, D. Hanahan, J. A. Joyce. 2006. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 20, 543-556 https://doi.org/10.1101/gad.1407406
  7. Hazen, L. G., F. E. Bleeker, B. Lauritzen, S. Bahns, J. Song, A. Jonker, Van B. E. Driel, H. Lyon, U. Hansen, A. Kohler, and Van C. J Noorden. 2000. Comparative localization of cathepsin B protein and activity in colorectal cancer. J. Histochem. Cytochem. 48, 1421-1430 https://doi.org/10.1177/002215540004801012
  8. Joyce, J. A., A. Baruch, K. Chehade, N. Meyer-Morse, E. Giraudo, F. Y. Tsai, D. C. Greenbaum, J. H. Hager, M. Bogyo, and D. Hanahan. 2004. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5, 443-453 https://doi.org/10.1016/S1535-6108(04)00111-4
  9. Keene, E. W., G. M. Petit, S. Allen, and H. J. McKerrow. 1986. The major neutral proteinase of Entamoeba histolytica. J. Exp. Med. 163, 536-549 https://doi.org/10.1084/jem.163.3.536
  10. Kirchke, H., R. Eerola, V. K. Hopsu-Havu, D. Bromme, and E. Vuorio. 2000. Antisense RNA inhibition of cathepsin L expression reduces tumorigenicity of malignant cells. Eur. J. Cancer. 36, 787-795 https://doi.org/10.1016/S0959-8049(00)00014-9
  11. Koblinski, J. E., M. Ahram, and B. F. Sloane. 2000. Unraveling the role of proteases in cancer. Clin. Chim. Acta. 291, 113-135 https://doi.org/10.1016/S0009-8981(99)00224-7
  12. Kos, J., B. Stabuc, A. Schweiger, M. Krasovec, N. Cimerman, N. Kopitar-Jeralla, and I. Vrhovec. 1997. Cathepsin B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clin. Cancer Res. 3, 1815-1822
  13. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685 https://doi.org/10.1038/227680a0
  14. Lah, T. T., M. Cercek, A. Blejec, J. Kos, E. Gorodetsky, R. Somers, and I. Daskal. 2000. Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. Clin. Cancer Res. 6, 578-584
  15. Leto, G., F. M. Tumminello, G. Pizzolanti, G. Montalto, M. Soresi, and N. Gebbia. 1997. Lysosomal cathepsins Band L blood level in patients with hepatocellular carcinoma and/ or liver cirrhosis: Potential clinical implications. Oncology 54, 79-83 https://doi.org/10.1159/000227666
  16. Ljusberg, J., Y. Wang, P. Lang, M. Norgard, R. Dodds, K. Hultenby, B. Ek-Rylander, and G. Andersson. 2005. Proteolytic excision of a repressive loop domain in tartrate-resistant acid phosphatase by cathepsin K in osteoclasts. J. BioI. Chem. 280, 28370-28381 https://doi.org/10.1074/jbc.M502469200
  17. Miyake, H., I. Hara, and H. Eto. 2004. Serum level of cathe psin B and its density in men with prostate cancer as novel markers of disease progression. Anticancer Res. 24, 2573-2577
  18. Nishikawa, H., Y. Ozaki, T. Nakanishi, K. Blomgren, T. Tada, A. Arakawa, and K. Suzumori. 2004. The role of cathepsin Band cystatin C in the mechanisms of invasion by ovarian cancer. Gynecol. Oncol. 92, 881-886 https://doi.org/10.1016/j.ygyno.2003.11.017
  19. Oh-e, H., S. Tanaka, Y. Kitadai, F. Shimamoto, M. Yoshihara, and K. Haruma. 2001. Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancer. Eur. J. Cancer 37, 180-188 https://doi.org/10.1016/S0959-8049(00)00348-8
  20. Puente, X. S., L. M. Sanchez, C. M. Overall, and C. Lopez-Otin. 2003. A genomic analysis of rat proteases and protease inhibitors. Nat. Rev. Genet. 4, 544-558 https://doi.org/10.1038/nrg1111
  21. Rochefort, H., M. Garcia, M. Glondu, V. Laurent, E. Liaudet, J. M. Rey, and P. Roger. 2000. Cathepsin D in breast cancer: Mechanisms and clinical applications, a 1999 overview. Clin. Chim. Acta. 291, 157-170 https://doi.org/10.1016/S0009-8981(99)00226-0
  22. Schmitt, M., F. Janicke, N. Moniwa, L. Chucholowski, H. Pache, and H Graeff. 1992. Tumor-associated urokinase-type plasminogen activator: Biological and clinical significance. BioI. Chem. Hoppe. Seyler 373, 611-622 https://doi.org/10.1515/bchm3.1992.373.2.611
  23. Shuja, S., J. Cai, C. Iacobuzio-Donahue, J. Zacks, R. M. Beazley, J. M. Kasznica, C. J. O'Hara, R. Heimann, and M. J. Murnane. 1999. Cathepsin B activity and protein levels in thyroid carcinoma, Graves' disease, and multinodular goiters. Thyroid 9, 569-577 https://doi.org/10.1089/thy.1999.9.569
  24. Shuja, S., and M. J. Murnane. 1996. Marked increases in cathepsin Band L activities distinguish papillary carcinomaof the thyroid from normal thyroid or thyroid with non-neoplastic disease. Int. J. Cancer 66, 420-426 https://doi.org/10.1002/(SICI)1097-0215(19960516)66:4<420::AID-IJC2>3.0.CO;2-Y
  25. Skrzydlewska, E., M. Sulkowska, M. Koda, and S. Sulkowski. 2005. Proteolytic-anti proteolytic balance and its regulation in carcinogenesis. World J. Gastroenterol. 11, 1251-1266 https://doi.org/10.1371/journal.pone.0000032
  26. Skrzydlewska, E., M. Sulkowska, A. Wincewicz, M. Koda, and S. Sulkowski. 2005. Evaluation of serum cathepsin B and D in relation to clinicopathological staging of colorectal cancer. World J. Gas troen terol. 11, 4225-4229
  27. Sloane, B. F. 1990. Cathepsin Band cystatins: Evidence for a role in cancer progression. Semin. Cancer BioI. 1, 137-152
  28. Towbin, H., and J. Gordon. 1984. Immunoblotting and dot immunoblotting; current status and outlook. J. Immunol. Methods 72, 313-318 https://doi.org/10.1016/0022-1759(84)90001-2
  29. Turk, B., D. Turk, and V. Turk. 2000. Lysosomes cysteine proteases; more that scavengers. Biochim. Biophys. Acta. 1477, 98-111 https://doi.org/10.1016/S0167-4838(99)00263-0
  30. van der Stappen, J. W., A. C. Williams, R. A. Maciewicz, and C. Paraskeva. 1996. Activation of cathepsin B, secreted by a colorectal cancer cell line requires low pH and is mediated by cathepsin D. Int. J. Cancer 67, 547-554 https://doi.org/10.1002/(SICI)1097-0215(19960807)67:4<547::AID-IJC14>3.0.CO;2-4
  31. Warwas, M., H. Haczynska, J. Gerber, and M. Nowak. 1997. Cathepsin B-like activity as a serum tumour marker in ovarian carcinoma. Eur. J. Clin. Chem. Clin. Biochem. 35, 301-304