Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography

Alejandro Curino; Vyomesh Patel; Boye S. Nielsen; Andrew J. Iskander; John F. Ensley; George H. Yoo; F. Christopher Holsinger; Jeffrey N. Myers; Adel El-Nagaar; Robert M. Kellman; Edward J. Shillitoe; Alfredo A. Molinolo; J. Silvio Gutkind; Thomas H. Bugge

doi:10.1016/j.oraloncology.2004.05.011

Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography

Alejandro Curino, Vyomesh Patel, Boye S. Nielsen, Andrew J. Iskander, John F. Ensley, George H. Yoo, F. Christopher Holsinger, Jeffrey N. Myers, Adel El-Nagaar, Robert M. Kellman, Edward J. Shillitoe, Alfredo A. Molinolo, J. Silvio Gutkind, Thomas H. Bugge

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 μg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

Original language	English (US)
Pages (from-to)	1026-1032
Number of pages	7
Journal	Oral Oncology
Volume	40
Issue number	10
DOIs	https://doi.org/10.1016/j.oraloncology.2004.05.011
State	Published - Nov 2004

Keywords

Laser capture microdissection
Oral cancer
Plasminogen activator
Plasminogen activator inhibitor
Squamous cell carcinoma
Urokinase
Zymography

ASJC Scopus subject areas

Oral Surgery
Oncology
Cancer Research

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10.1016/j.oraloncology.2004.05.011

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Curino, A., Patel, V., Nielsen, B. S., Iskander, A. J., Ensley, J. F., Yoo, G. H., Holsinger, F. C., Myers, J. N., El-Nagaar, A., Kellman, R. M., Shillitoe, E. J., Molinolo, A. A., Gutkind, J. S., & Bugge, T. H. (2004). Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography. Oral Oncology, 40(10), 1026-1032. https://doi.org/10.1016/j.oraloncology.2004.05.011

Curino, A, Patel, V, Nielsen, BS, Iskander, AJ, Ensley, JF, Yoo, GH, Holsinger, FC, Myers, JN , El-Nagaar, A, Kellman, RM, Shillitoe, EJ, Molinolo, AA, Gutkind, JS & Bugge, TH 2004, 'Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography', Oral Oncology, vol. 40, no. 10, pp. 1026-1032. https://doi.org/10.1016/j.oraloncology.2004.05.011

@article{f7f8242f5b55494f80b25579ebacfddd,

title = "Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography",

abstract = "Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 μg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.",

keywords = "Laser capture microdissection, Oral cancer, Plasminogen activator, Plasminogen activator inhibitor, Squamous cell carcinoma, Urokinase, Zymography",

author = "Alejandro Curino and Vyomesh Patel and Nielsen, {Boye S.} and Iskander, {Andrew J.} and Ensley, {John F.} and Yoo, {George H.} and Holsinger, {F. Christopher} and Myers, {Jeffrey N.} and Adel El-Nagaar and Kellman, {Robert M.} and Shillitoe, {Edward J.} and Molinolo, {Alfredo A.} and Gutkind, {J. Silvio} and Bugge, {Thomas H.}",

note = "Funding Information: We thank Charlotte L{\o}nborg for excellent technical assistance, and Dr. Mary Jo Danton for critically reading this manuscript. BSN is a recipient of a grant from the Weimann Foundation, Copenhagen, Denmark.",

year = "2004",

month = nov,

doi = "10.1016/j.oraloncology.2004.05.011",

language = "English (US)",

volume = "40",

pages = "1026--1032",

journal = "Oral Oncology",

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publisher = "Elsevier Limited",

number = "10",

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T1 - Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography

AU - Curino, Alejandro

AU - Patel, Vyomesh

AU - Nielsen, Boye S.

AU - Iskander, Andrew J.

AU - Ensley, John F.

AU - Yoo, George H.

AU - Holsinger, F. Christopher

AU - Myers, Jeffrey N.

AU - El-Nagaar, Adel

AU - Kellman, Robert M.

AU - Shillitoe, Edward J.

AU - Molinolo, Alfredo A.

AU - Gutkind, J. Silvio

AU - Bugge, Thomas H.

N1 - Funding Information: We thank Charlotte Lønborg for excellent technical assistance, and Dr. Mary Jo Danton for critically reading this manuscript. BSN is a recipient of a grant from the Weimann Foundation, Copenhagen, Denmark.

PY - 2004/11

Y1 - 2004/11

N2 - Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 μg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

AB - Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 μg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

KW - Laser capture microdissection

KW - Oral cancer

KW - Plasminogen activator

KW - Plasminogen activator inhibitor

KW - Squamous cell carcinoma

KW - Urokinase

KW - Zymography

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M3 - Article

C2 - 15509494

AN - SCOPUS:7044285790

SN - 1368-8375

VL - 40

SP - 1026

EP - 1032

JO - Oral Oncology

JF - Oral Oncology

IS - 10

ER -

Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography

Abstract

Keywords

ASJC Scopus subject areas

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