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Significance of Elevated Levels of Collagen Type IV and Hyaluronic Acid in Gastric Juice and Serum in Gastric Cancer and Precancerous Lesion

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Abstract

Background and Aims

Collagen type IV and hyaluronic acid (HA) are the major components of basement membrane and extracellular matrix, respectively. Cathepsin D is an aspartyl lysosomal protease involved in the degradation of the basement membrane and extracellular matrix. The aim of this study is to investigate the clinical significance of collagen type IV and hyaluronic acid in gastric juice and serum in diagnosis of gastric cancer and the degrading effect of cathepsin D on collagen type IV and HA.

Methods

Fifty gastric cancer patients were enrolled in our study compared with 41 patients with precancerous lesion and 30 control subjects. Collagen type IV and HA in gastric juice and serum were analyzed by radioimmunoassay. Expression of cathepsin D and collagen type IV in tissue were analyzed by immunohistochemical staining with monoclonal antibodies.

Results

The contents of collagen type IV and HA in gastric juice and HA in serum were significantly higher in patients with gastric cancer than those in patients with precancerous lesion and control group (p < 0.05, p < 0.0001). Gastric cancer patients with lymph node metastasis had a higher level of collagen type IV and HA in gastric juice than those in patients without metastasis (p = 0.049, p = 0.043). The expression of cathepsin D had significantly increased in patients with gastric cancer compared to the control group (p < 0.0001). The continuous expression of collagen type IV in basement membrane in gastric cancer group was lower than that in the precancerous lesion group and control group (p < 0.0001).

Conclusions

The analysis of collagen type IV and HA in gastric juice and serum may provide a simple aid in diagnosing gastric cancer and evaluating whether metastasis is occurring or not.

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References

  1. Bertuccio P, Chatenoud L, Levi F, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125:666–673.

    Article  PubMed  CAS  Google Scholar 

  2. Charalabopoulos K, Mittari E, Karakosta A, Golias C, Batistatou A. Integrins adhesion molecules and some of their ligands in laryngeal cancer. Exp Oncol. 2005;27:86–90.

    PubMed  CAS  Google Scholar 

  3. Dragutinović V, Izrael-Zivković L, Radovanović N. Relation of matrix metalloproteinase-9 to different stages of tumors in the serum of gastric cancer. Dig Dis Sci. 2009;54:1203–1207.

    Article  PubMed  Google Scholar 

  4. Mazouni C, Arun B, André F, et al. Collagen IV levels are elevated in the serum of patients with primary breast cancer compared with healthy volunteers. Br J Cancer. 2008;99:68–71.

    Article  PubMed  CAS  Google Scholar 

  5. Setälä LP, Tammi MI, Tammi RH, et al. Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate. Br J Cancer. 1999;79:1133–1138.

    Article  PubMed  Google Scholar 

  6. Abbott DE, Margaryan NV, Jeruss JS, et al. Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology. Cancer Biol Ther. 2010;9:23–30.

    Article  PubMed  Google Scholar 

  7. Yeh JM, Hur C, Kuntz KM, Ezzati M, Goldie SJ. Cost-effectiveness of treatment and endoscopic surveillance of precancerous lesions to prevent gastric cancer. Cancer. 2010;116:2941–2953.

    Article  PubMed  Google Scholar 

  8. Baba Y, Iyama K, Ikeda K, et al. Differential expression of basement membrane type IV collagen alpha chains in gastric intramucosal neoplastic lesions. J Gastroenterol. 2007;42:874–880.

    Article  PubMed  CAS  Google Scholar 

  9. Allgayer H, Babic R, Grützner KU, et al. An immunohistochemical assessment of cathepsin D in gastric carcinoma: its impact on clinical prognosis. Cancer. 1997;80:179–187.

    Article  PubMed  CAS  Google Scholar 

  10. Szumilo J, Burdan F, Zinkiewicz K, et al. Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma. Folia Histochem Cytobiol. 2009;47:571–578.

    Article  PubMed  Google Scholar 

  11. Hewitt RE, Powe DG, Carter GI, Turner DR, Price JE. Basement membrane collagen-IV synthesis in colorectal tumors. Int J Cancer. 1992;51:530–536.

    Article  PubMed  CAS  Google Scholar 

  12. Tanjore H, Kalluri R. The role of type IV collagen and basement membranes in cancer progression and metastasis. Am J Pathol. 2006;168:715–717.

    Article  PubMed  CAS  Google Scholar 

  13. ACh Lazaris, Tzoumani AN, Thimara I, et al. Immunohistochemical assessment of basement membrane components in colorectal cancer: prognostic implications. J Exp Clin Cancer Res. 2003;22:599–606.

    Google Scholar 

  14. Marasà L, Marasà S, Sciancalepore G, Collagen IV. laminin, fibronectin, vitronectin. Comparative study in basal cell carcinoma. Correlation between basement membrane molecules expression and invasive potential. G Ital Dermatol Venereol. 2008;143:169–173.

    PubMed  Google Scholar 

  15. Ohlund D, Lundin C, Ardnor B, Oman M, Naredi P, Sund M. Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer. Br J Cancer. 2009;101:91–97.

    Article  PubMed  CAS  Google Scholar 

  16. Mazouni C, Arun B, André F, Collagen IV, et al. Levels are elevated in the serum of patients with primary breast cancer compared with healthy volunteers. Br J Cancer. 2008;99:68–71.

    Article  PubMed  CAS  Google Scholar 

  17. Korenaga D, Orita H, Maekawa S, Itasaka H, Ikeda T, Sugimachi K. Peritoneal collagen type IV concentration in adenocarcinoma of the gastrointestinal tract and its relationship to histological differentiation, metastasis, and survival. Surg Today. 1998;28:780–786.

    Article  PubMed  CAS  Google Scholar 

  18. McDonald JA, Camenisch TD. Hyaluronan: genetic insights into the complex biology of a simple polysaccharide. Glycoconj J. 2002;19:331–339.

    Article  PubMed  CAS  Google Scholar 

  19. Auvinen P, Tammi R, Parkkinen J, et al. Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival. Am J Pathol. 2000;156:529–536.

    Article  PubMed  CAS  Google Scholar 

  20. Bharadwaj AG, Kovar JL, Loughman E, Elowsky C, Oakley GG, Simpson MA. Spontaneous metastasis of prostate cancer is promoted by excess hyaluronan synthesis and processing. Am J Pathol. 2009;174:1027–1036.

    Article  PubMed  Google Scholar 

  21. Gomez CS, Gomez P, Knapp J, Jorda M, Soloway MS, Lokeshwar VB. Hyaluronic acid and HYAL-1 in prostate biopsy specimens: predictors of biochemical recurrence. J Urol. 2009;182:1350–1356.

    Article  PubMed  Google Scholar 

  22. Vizoso FJ, del Casar JM, Corte MD, et al. Significance of cytosolic hyaluronan levels in gastric cancer. Eur J Surg Oncol. 2004;30:318–324.

    PubMed  CAS  Google Scholar 

  23. Paiva P, Van Damme MP, Tellbach M, Jones RL, Jobling T, Salamonsen LA. Expression patterns of hyaluronan, hyaluronan synthases and hyaluronidases indicate a role for hyaluronan in the progression of endometrial cancer. Gynecol Oncol. 2005;98:193–202.

    Article  PubMed  CAS  Google Scholar 

  24. Gao ZL, Zhang C, Du GY, Lu ZJ. Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma. Hepatogastroenterology. 2007;54:1591–1595.

    PubMed  CAS  Google Scholar 

  25. Yabushita H, Kishida T, Fusano K, et al. Role of hyaluronan and hyaluronan synthase in endometrial cancer. Oncol Rep. 2005;13:1101–1105.

    PubMed  CAS  Google Scholar 

  26. Zaidi N, Maurer A, Nieke S, Kalbacher H. Cathepsin D: a cellular roadmap. Biochem Biophys Res Commun. 2008;376:5–9.

    Article  PubMed  CAS  Google Scholar 

  27. Hu L, Roth JM, Brooks P, Luty J, Karpatkin S. Thrombin up-regulates cathepsin D which enhances angiogenesis, growth, and metastasis. Cancer Res. 2008;68:4666–4673.

    Article  PubMed  CAS  Google Scholar 

  28. Szajda SD, Snarska J, Jankowska A, Roszkowska-Jakimiec W, Puchalski Z, Zwierz K. Cathepsin D and carcino-embryonic antigen in serum, urine and tissues of colon adenocarcinoma patients. Hepatogastroenterology. 2008;55:388–393.

    PubMed  CAS  Google Scholar 

  29. Szajda SD, Snarska J, Roszkowska-Jakimiec W, et al. Activity of cathepsin D in the blood serum and urine of patients with cancer of the stomach, pancreas and liver. Pol Arch Med Wewn. 2006;116:1150–1154.

    PubMed  CAS  Google Scholar 

  30. Ikeguchi M, Fukuda K, Oka S, et al. Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma. Oncology. 2001;61:71–78.

    Article  PubMed  CAS  Google Scholar 

  31. García I, Vizoso F, Suárez C, et al. Relationship of tumoral hyaluronic acid and cathepsin D contents with histological type of gastric carcinoma. Int J Biol Markers. 2000;15:215–218.

    PubMed  Google Scholar 

  32. Goishi H, Tanaka S, Haruma K, et al. Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer. Oncol Rep. 2000;7:713–718.

    PubMed  CAS  Google Scholar 

  33. Ikeguchi M, Fukuda K, Oka S, et al. Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer. J Surg Oncol. 2001;77:188–194.

    Article  PubMed  CAS  Google Scholar 

  34. Leto G, Tumminello FM, Crescimanno M, Flandina C, Gebbia N. Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. Clin Exp Metastasis. 2004;21:91–106.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Department of Nuclear Medicine and Key Laboratory of the First Affiliated Hospital of Anhui Medical University.

Conflicts of interest

All authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province, Hefei, 230022, Anhui Province, China

    Hai-Ling Ruan, Ru-Tao Hong, Hui-Jun Xie, Nai-Zhong Hu, Jian-Ming Xu & Wei Zhang

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  1. Hai-Ling Ruan
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  2. Ru-Tao Hong
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  3. Hui-Jun Xie
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Correspondence to Ru-Tao Hong.

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Ruan, HL., Hong, RT., Xie, HJ. et al. Significance of Elevated Levels of Collagen Type IV and Hyaluronic Acid in Gastric Juice and Serum in Gastric Cancer and Precancerous Lesion. Dig Dis Sci 56, 2001–2008 (2011). https://doi.org/10.1007/s10620-011-1571-8

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  • DOI: https://doi.org/10.1007/s10620-011-1571-8

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