Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers
Section snippets
Gelatinases and their inhibitors in breast carcinoma
Breast cancer is the most common female malignant tumor in the western world. The overall prognosis of breast cancer patients has improved during the last decade. Despite the fact that this neoplasia is potentially fatal, several patients still have a more indolent clinical course of the disease, and these patients often have favorable survival. Many biological factors associated with progression or aggressive behavior of cancer have been identified to help distinguish the aggressive disease,
MMP-2 and -9 in gynecological neoplasias
Preclinical studies have linked the activity of the matrix metalloproteinases with aggressive behavior in ovarian carcinoma [8], [9], [47]. Metalloproteinases and their mRNA have been localized both to tumor cells and to stromal fibroblasts in ovarian carcinoma [48]. It is possible that ovarian cancer cells are dependent on stromal interactions in their MMP expression [8], [9]. Cultured ovarian cancer cells are able to maintain MMP-2 expression after primary cultures when MMP-9 expression
Gelatinases and their inhibitors in prostatic neoplasia
In preclinical studies, MMP-9 has been linked to the ability of cultured prostate carcinoma cells to produce lung metastases in animal models [64]. It is probable that both MMP-2 and -9 play a role in prostate cancer cell invasion [65] as well as in prostate cancer-induced angiogenesis [66]. The gelatinases associate with the progression of prostatic neoplasia in several clinical studies [67], [68], [69], [70]. The MT1-MMP and MMP-2 immunolocalization have been shown to change during the
Metalloproteinases and their inhibitors in bladder and renal carcinomas
Many preclinical studies have explored the role of the metalloproteinases in cancer invasion by using bladder transitional cell carcinoma cells as a model. Recent clinical studies have confirmed the preclinical findings suggesting that gelatinases seem at least to be linked with the progression of transitional cell carcinoma of the bladder. Inverse association with TIMP-2 and survival has been shown in bladder cancer by Grignon et al. (1996) [74]. The expression of MMP-2, MT1 MMP as well as
Markers of matrix degradation in lung carcinoma
Lung carcinoma is a common and very aggressive neoplasm including histologically different entities with unfavorable prognosis. The number of studies suggesting that MMPs may be involved in lung cancer progression is increasing. Bronchopulmonary carcinomas overexpress the mRNA for MMP-2, MT1-MMP and MMP-11, especially when presenting with a malignant phenotype and high tumor stage [81]. The MMP-2 and -9 have been associated with increased tumor spread and poor prognosis in lung cancer [82], [83]
Gelatinases in head and neck carcinomas
Head and neck cancers consist of a heterogeneous group of neoplasias, 90% of which are squamous cell carcinomas (HNSCC). Clinical stage at the time of diagnosis and anatomic region are naturally the most important predictors of survival, but the clinical behavior of these tumors varies and might be attributed to the biological factors involved in growth and invasion. Elevated levels of the immunoreactive protein for MMP-2 and -9 have been detected in nearly 40% of HNSCC tumors [89]. MMP-9, but
MMPs and their inhibitors in gastrointestinal cancers
Both MMP-2 and -9 have been shown to correlate with malignant behavior in various gastrointestinal tumors. In colorectal carcinoma, positive correlation has been reported between high expression of MMP-2 or TIMP-2 and advanced stage [92], [93] as well as between MMP-9 mRNA and early relapse or poor survival [94]. The TIMP-1 also seems to associate with aggressive phenotype in colorectal carcinoma, circulating TIMP being high in patients presenting with lymph node or liver metastases of
MMP-2 and -9 in melanoma
Different murine and human melanoma cell lines and tumors have been widely used as preclinical models in studying invasion and metastasis in general. These studies address the role of different MMPs in melanoma progression. Cultured melanoma cells have been shown to produce at least MMP-1, -2, -3 and -9, and the MMP-activity has been correlated with melanoma invasion [102], [103], [104], [105], [106]. The expression of MMP-2 and -9 as well as the invasion and attachment is modified in cultured
Gelatinases in brain neoplasias
The treatment of the most aggressive forms of brain tumors still poses a challenge. In spite of the development of new drugs, the prognosis of aggressive gliomas is still poor. New options for treatment would thus be welcome. It is typical that brain neoplasms vary in their ability to invade surrounding tissues and recur after radical treatment. The most malignant brain tumors (glioblastoma multiforme) are fairly resistant to therapy and cause death in due course, while low malignancy tumors
Summary
Clinical data in several solid cancers show that gelatinases generally associate with aggressive clinical course of the disease. However, the impact of this association seems to vary in different solid cancer diseases. Given the fact that there is a great deal of variation in both the biological features and the clinical course between the distinct neoplastic diseases, it is surprising that particularly MMP-2 seems to associate with an aggressive clinical course in a large variety of solid
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