Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients

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Authors

HALÁMKOVÁ Jana KISS Igor PAVLOVSKÝ Zdeněk TOMÁŠEK Jiří JARKOVSKÝ Jiří ČECH Zbyněk TUČEK Štěpán HANÁKOVÁ L. MOULIS Mojmír ZAVŘELOVÁ J. MAN M. BENDA Petr ROBEK Oldřich KALA Zdeněk PENKA Miroslav

Year of publication 2011
Type Article in Periodical
Magazine / Source Neoplasma
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.4149/neo_2011_05_377
Field Oncology and hematology
Keywords colorectal cancer; plasminogen activator system; grade; treatment response
Description Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma.

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