Urokinase-Type Plasminogen Activator Expression and Proliferation Stimulation in Head and Neck Squamous Cell Carcinoma In Vitro and In Situ | Cancer Biomarkers | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Article
June 2001

Urokinase-Type Plasminogen Activator Expression and Proliferation Stimulation in Head and Neck Squamous Cell Carcinoma In Vitro and In Situ

Author Affiliations

From the Department of Otorhinolaryngology, University of Wuerzburg, Wuerzburg, Germany.

Arch Otolaryngol Head Neck Surg. 2001;127(6):679-682. doi:10.1001/archotol.127.6.679

Background  Stimulation of proliferative activity by urokinase-type plasminogen activator (uPA) has been demonstrated in vitro for cultured primary and carcinoma cells.

Objective  To examine the effect of uPA stimulation on cultured squamous cell carcinoma cell lines of the head and neck in vitro and to compare the results with the situation in tumor tissue specimens.

Design  The uPA-mediated growth stimulation of 2 head and neck squamous cell carcinoma cell lines after suppression of endogenous uPA production was monitored by measuring 3H-thymidine uptake into cellular DNA. Alternatively, applications of antibodies against the uPA-binding domain of the urokinase receptor were used to suppress autostimulation. To analyze the situation in situ we performed Western blot and zymographic studies on tissue homogenates of 25 squamous cell carcinoma specimens. We tested the expression of proliferating cell nuclear antigen (PCNA), a marker for proliferative activity, and uPA in tissue lysates and correlated uPA and PCNA expression by regression analysis.

Results  High-molecular-weight urokinase had a proliferation stimulative effect on both cell lines in vitro. The uPA autostimulation was decreased by blocking the uPA-binding domain of urokinase receptor with antibodies. Regression analysis of zymographic and Western blot data of tumor tissue lysates revealed no significant coherency between PCNA and uPA expression. Immunohistochemical stainings frequently showed different sublocalization of uPA and PCNA within tumors.

Conclusion  In vitro uPA-mediated growth stimulation is not necessarily transferable to the in situ situation.