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

研究成果: 雜誌貢獻文章同行評審

112 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)6537-6542
頁數6
期刊Cancer Research
63
發行號19
出版狀態已發佈 - 十月 1 2003
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

指紋 深入研究「Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer」主題。共同形成了獨特的指紋。

引用此