Changes in Matrix Metalloproteinases and Their Endogenous Inhibitors During Tumor Progression in the Uterine Cervix

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2003 Apr 2

PMID 12669237

Citations 13

Authors

S Asha Nair

D Karunagaran

M B Nair

P R Sudhakaran

Affiliations

Soon will be listed here.

Abstract

Purpose: To study the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cervical tumorigenesis, we analyzed 70 cervical tissue specimens that included 15 low-grade squamous intraepithelial lesions (SILs), 20 high-grade SILs, 25 squamous cell carcinomas (SCCs) and 10 specimens of normal cervical tissue.

Methods: The gelatinolytic activity of MMP-9 and MMP-2 was determined by zymographic analysis. The expression of MMP-9 and MMP-2 and TIMP-1 and TIMP-2 was determined by immunohistochemistry.

Results: All the samples had 72/66 kDa gelatinase activity; 92 kDa gelatinase activity was detected only in high-grade SILs and SCCs. Immunohistochemical analysis showed weak positivity for MMP-2 in normal cervical epithelium and low-grade SILs. However, high-grade SILs and SCCs showed intense cellular and stromal reactivity for MMP-2 and MMP-9. For TIMP-1 and TIMP-2, normal cervical epithelium and low-grade SILs showed intense immunostaining, >50% of high-grade SILs showed positivity, and 95% of SCCs showed intense stromal and cellular reactivity.

Conclusions: Increase in the relative activity of these gelatinases and enhanced immunostaining for MMPs and TIMPs with tumor progression suggest that they may play a crucial role in cervical cancer progression. A significant association between stage of the lesion and expression of MMPs and TIMPs ( P<0.01) was found. Immunohistochemical studies indicate that these MMPs may be of basal cell origin in cervical tissue, although the mechanism of their upregulation is not clearly understood.

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