Hyaluronidases and their inhibitors in the serum of colorectal carcinoma patients

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Abstract

Colorectal cancer is the third most commonly diagnosed type of cancer. Hyaluronan is involved in this malignancy. Moreover, hyaluronidases – its degrading enzymes – display controversial roles regarding their involvement in tumor development. HYAL-1 is the major tumor derived hyaluronidase. The aim of the study was the determination and evaluation of hyaluronidase levels in serum of colorectal cancer patients, before and after surgery, with a view to assessing its potential role as a tumor marker for recurrence. By zymography and Western blotting, it was confirmed that HYAL-1 was the only hyaluronidase present in samples. Quantification of its activity indicated a statistically significant decrease in samples seven days postoperatively, compared with the respective ones before surgery. HYAL-1 levels before surgery were significantly reduced in comparison with healthy samples and samples one year postoperatively. Hyaluronidase inhibitor activity was demonstrated under mild alkaline conditions via reverse zymography. A statistically significant increase was observed in samples seven days postoperatively, when compared with samples before surgery. HYAL-1 levels in sera of colorectal cancer patients were lower than those of healthy population, possibly because of the local accumulation of the enzyme in tumor microenvironment. A gradual elevation up to one year postoperatively to reach healthy levels might indicate a role of HYAL-1 levels in cancer.

Graphical abstract

HYAL-1 activity in sera of CRC patients: Quantification of HYAL-1 activity (buffer pH 3.7) in sera obtained from normal population (N) and CRC patients one day before operation (D-1), one week (D + 7) and one year (D + Y) postoperatively. Single asterisk indicates statistical difference with normal population (p < 0.05). Double asterisk indicates statistical difference with sera obtained one day preoperatively (p < 0.01).

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