Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer

Bor Ching Sheu, Huang Chun Lien, Hong Nerng Ho, Ho Hsiung Lin, Song Nan Chow, Su Cheng Huang, Su Ming Hsu

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.

Original languageEnglish
Pages (from-to)6537-6542
Number of pages6
JournalCancer Research
Volume63
Issue number19
Publication statusPublished - Oct 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer. / Sheu, Bor Ching; Lien, Huang Chun; Ho, Hong Nerng; Lin, Ho Hsiung; Chow, Song Nan; Huang, Su Cheng; Hsu, Su Ming.

In: Cancer Research, Vol. 63, No. 19, 01.10.2003, p. 6537-6542.

Research output: Contribution to journalArticle

Sheu, Bor Ching ; Lien, Huang Chun ; Ho, Hong Nerng ; Lin, Ho Hsiung ; Chow, Song Nan ; Huang, Su Cheng ; Hsu, Su Ming. / Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer. In: Cancer Research. 2003 ; Vol. 63, No. 19. pp. 6537-6542.
@article{4db85e9214e64d3ea70144c46e146a76,
title = "Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer",
abstract = "Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90{\%} of squamous cell carcinomas (SCC) and 83-100{\%} of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13{\%}). MMP-1, MMP-14, and MMP-15 were detected in 55-81{\%} of SCC cases, and MMP-1 was detected in 39{\%} of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61{\%}). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.",
author = "Sheu, {Bor Ching} and Lien, {Huang Chun} and Ho, {Hong Nerng} and Lin, {Ho Hsiung} and Chow, {Song Nan} and Huang, {Su Cheng} and Hsu, {Su Ming}",
year = "2003",
month = "10",
day = "1",
language = "English",
volume = "63",
pages = "6537--6542",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

TY - JOUR

T1 - Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer

AU - Sheu, Bor Ching

AU - Lien, Huang Chun

AU - Ho, Hong Nerng

AU - Lin, Ho Hsiung

AU - Chow, Song Nan

AU - Huang, Su Cheng

AU - Hsu, Su Ming

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.

AB - Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.

UR - http://www.scopus.com/inward/record.url?scp=0141953315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141953315&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 6537

EP - 6542

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 19

ER -