Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

Abstract

Rauvala M, Aglund K, Puistola U, Turpeenniemi-Hujanen T, Horvath G, Willén R, Stendahl U. Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression. Int J Gynecol Cancer 2006;16:1297-1302.The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.

The role of Twist1 in hepatocellular carcinoma angiogenesis: a clinical study

“…MMPs act as critical mediators of the EMT process, thus degrading and remodeling extracellular matrix, stimulating cell proliferation and apoptosis, and inducing cell migration and cell morphological alterations [11,[35][36][37]. In this study, we detected high-level expressions of MMP-2 and MMP-9 in HCC, but only MMP-9 was associated and correlated with MVD counts and survival period.…”

Uterine cervical carcinoma: Role of matrix metalloproteinases (Review)

“…During the last decades progress in research on enzyme activities showed the potential significance of MMP-2 and MMP-9 in the progression of cervical uterine cancer suggesting their prognostic value (14,15,(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65). Sheu et al demonstrated that MMP-2 and MMP-9 were overexpressed in >90% of squamous cell carcinomas (SCC) and 83-100% of HSIL, but were less frequently expressed in LSIL and normal squamous epithelium (13%).…”

High Resolution Proteomic Analysis of the Cervical Cancer Cell Lines Secretome Documents Deregulation of Multiple Proteases

“…In a study that included primary tumors with stages of increasing severity, MMP-2 expression was up-regulated in advanced stage tumors, whereas ΜΜP-9 displayed the highest expression in tumors of early stages. The above observation probably reflects the differential roles of MMP-2 and MMP-9 in oncogenesis, where basically MMP-2 is up-regulated during oncogenesis, while MMP-9 has been shown to be downregulated after stage I (35).…”

“…MMP-2 and MMP-9 types degrade proteoglycan and nonproteoglycan components of extracellular matrix, like collagen IV and laminin-5. Extracellular matrix degradation facilitates the detachment of cancer cells from the primary tumor and the initiation of metastasis (35,36). ΜΜPs regulated by their inhibitors ΤΙΜPs (37) are generally up-regulated in cancer tissues and contribute to oncogenesis (35).…”

“…Extracellular matrix degradation facilitates the detachment of cancer cells from the primary tumor and the initiation of metastasis (35,36). ΜΜPs regulated by their inhibitors ΤΙΜPs (37) are generally up-regulated in cancer tissues and contribute to oncogenesis (35). As far as cervical cancer is concerned, there are conflicting data in the literature.…”