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
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.170.64.36. Please contact the publisher to request reinstatement.
1.
Andreasen  PAKjoller  LChristensen  L  et al The urokinase-type plasminogen activator system in cancer metastasis: a review.  Int J Cancer.1997;72:1-22.Google Scholar
2.
Kirchheimer  JCWojta  JChrist  G  et al Proliferation of a human epidermal tumor cell line stimulated by urokinase.  FASEB J.1987;1:125-128.Google Scholar
3.
Kirchheimer  JCWojta  JChrist  G  et al Mitogenic effect of urokinase on malignant and unaffected adjacent human renal cells.  Carcinogenesis.1988;9:2121-2123.Google Scholar
4.
Kirchheimer  JCWojta  JHienert  G  et al Effect of urokinase on the proliferation of primary cultures of human prostatic cells.  Thromb Res.1987;48:291-298.Google Scholar
5.
Schmidt  MPolednik  CHoppe  F Proteolytic patterns in head and neck squamous cell carcinoma.  Eur Arch Otorhinolaryngol.1999;256:346-350.Google Scholar
6.
Clayman  GWang  SWNicolson  GL  et al Regulation of urokinase-type plasminogen activator expression in squamous-cell carcinoma of the oral cavity.  Int J Cancer.1993;54:73-80.Google Scholar
7.
Zenner  HPHerrmann  IFBremer  W  et al Head and neck carcinoma models.  Acta Otolaryngol.1983;95:371-381.Google Scholar
8.
Zenner  HPLehner  WHerrmann  IF Establishment of carcinoma cell lines from larynx and submandibular gland.  Arch Otorhinolaryngol.1979;225:269-277.Google Scholar
9.
Fischer  KLutz  VWilhelm  O  et al Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function.  FEBS Lett.1998;438:101-105.Google Scholar
10.
Lowry  OHRosebrough  NNJFarr  AL  et al Protein measurement with the Folin phenol reagent.  J Biol Chem.1951;193:265-275.Google Scholar
11.
Heussen  DDowdle  EB Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates.  Anal Biochem.1980;102:196-202.Google Scholar
12.
Kyhse-Andersen  J Electroblotting of multiple gels: a simple apparatus without tank for rapid transfer of proteins from polyacrylamide to nitrocellulose.  J Biochem Biophys Methods.1984;10:203-210.Google Scholar
13.
Schmidt  MSchler  GGrünsfelder  PMuller  JHoppe  F Urokinase receptor up-regulation in head and neck squamous cell carcinoma.  Head Neck.2000;22:498-504.Google Scholar
14.
Kirchheimer  JCWojta  JChrist  G  et al Functional inhibition of endogenously produced urokinase decreases cell proliferation in a human melanoma cell line.  Proc Natl Acad Sci U S A.1989;86:5424-5428.Google Scholar
15.
Jensen  PJLavker  RM Urokinase is a positive regulator of epidermal proliferation in vivo.  J Invest Dermatol.1999;112:240-244.Google Scholar
16.
Gohring  UJScharl  AThelen  UAhr  ATitius  BR Prognostic value of immunohistochemical determination of urokinase type plasminogen activator in primary breast cancers.  Pathologe.1995;16:398-403.Google Scholar
17.
Volm  MMattern  JKoomägi  R Relationship of urokinase and urokinase receptor in non–small cell lung cancer to proliferation, angiogenesis, metastasis and patient survival.  Oncol Rep.1999;6:611-615.Google Scholar
18.
Hibino  TMatsuda  YTakahashi  T  et al Suppression of keratinocyte proliferation by plasminogen activator inhibitor-2.  J Invest Dermatol.1999;112:85-90.Google Scholar
19.
Fishman  DAKearns  ALarsh  S  et al Autocrine regulation of growth stimulation in human epithelial ovarian carcinoma by serine-proteinase–catalysed release of the urinary-type plasminogen-activator N-terminal fragment.  Biochem J.1999;341:765-769.Google Scholar
20.
Morita  YHayashi  YKanamaru  T  et al Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells.  Jpn J Cancer Res.1999;90:747-752.Google Scholar
21.
Wollenberg  BJan  NVJund  RChaubal  SUntch  M Urokinase-type plasminogen activator and its inhibitor plasminogen activator inhibitor-1: new functional risk factors in head and neck squamous cell cancer.  Oncol Rep.1997;48:53-55.Google Scholar
22.
Rabbani  SAMazar  APBernier  SM  et al Structural requirements for the growth factor activity of the aminoterminal domain of urokinase.  J Biol Chem.1992;267:14151-14156.Google Scholar
23.
Schmidt  MHoppe  F Increased levels of urokinase receptor in plasma of head and neck squamous cell carcinoma patients.  Acta Otolaryngol (Stockh).1999;119:949-953.Google Scholar
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
Abstract

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.

×