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Open Access Research article

Involvement of hyaluronidases in colorectal cancer

Helen Bouga1, Isidoros Tsouros1, Dimitrios Bounias2, Dora Kyriakopoulou2, Michael S Stavropoulos2, Nikoletta Papageorgakopoulou1, Dimitrios A Theocharis3 and Demitrios H Vynios1*

Author Affiliations

1 Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece

2 Department of Surgery, University Hospital, Patras, Greece

3 Laboratory of Biological Chemistry, Department of Medicine, University of Patras, Patras, Greece

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BMC Cancer 2010, 10:499  doi:10.1186/1471-2407-10-499

Published: 17 September 2010

Abstract

Background

Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size. The aim of the present study was therefore to illuminate the importance of hyaluronidases in colon carcinoma progression.

Methods

The patients' samples (macroscopically normal and cancerous) were subjected to sequential extraction with PBS, 4 M GdnHCl and 4 M GdnHCl - 1% Triton X-100. The presence of the various hyaluronidases in the extracts was examined by zymography and western blotting. Their expression was also examined by RT-PCR.

Results

Among hyaluronidases examined, Hyal-1, -2, -3 and PH-20 were detected. Their activity was higher in cancerous samples. Hyal-1 and Hyal-2 were overexpressed in cancerous samples, especially in advanced stages of cancer. Both isoforms were mainly extracted with PBS. Hyal-3 was observed only in the third extract of advanced stages of cancer. PH-20 was abundant in all three extracts of all stages of cancer. The expression of only Hyal-1 and PH-20 was verified by RT-PCR.

Conclusion

A high association of hyaluronidases in colorectal cancer was observed. Each hyaluronidase presented different tissue distribution, which indicated the implication of certain isoforms in certain cancer stages. The results provided new evidence on the mechanisms involved in the progression of colorectal cancer.