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Abstract

Sixty human brain tumors, classified according to the New World Health Organization (WHO) classification including, grade I schwannomas, meningiomas and pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astrocytomas, grade IV glioblastomas, grade III anaplastic oligodendrogliomas and grade IV glioblastomas and lung and melanoma metastases were analyzed for the expression of three matrix metalloproteinases (MMPs), two tissue inhibitors of MMPs (TIMPs) and for MMP activity. Some correlation was found between MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) than of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. MMP-9 levels were found to be significantly higher in grade III anaplastic astrocytomas and anaplastic oligodendrogliomas than those in grade I schwannomas and meningiomas. Anaplastic astrocytomas and Grade IV glioblastomas expressed significantly higher levels MMP-12 than grade I meningiomas. All sixty tumors showed a similar pattern of activity in zymography, proMMP-9 being the major species detected. Interestingly, TIMP-1 and TIMP-2 expression levels were especially low in tumors of grade II and grade III but significantly higher in tumors of grade I, particularly in schwannomas. Taken together, these data suggest that: 1) a balance between MMPs and TIMPs has an important role to play in human brain tumors; 2) TIMP expression may be valuable markers for tumor malignancy.

Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2

“…MMP-2 has been demonstrated to be expressed in numerous tumor types (31) and also in diseases that involve tissue remodeling (44). However, MMP-2 appears to be a major matrix metalloproteinase in gliomas (27) and is absent from normal brain tissue (45,46). Hence, the finding that MMP-2 is the principal receptor for Cltx is consistent with the recent finding that the Cltx receptor is primarily expressed in glioma and tumors of neuroectodermal origin (18).…”

Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis

“…Gelatinase activity also appeared to be increased in malignant tissues as compared to low grade and normal brain tissue (Rao et al, 1993(Rao et al, , 1996Kachra et al, 1999).…”

Clinicopathological Significance of Human Macrophage Metalloelastase Expression in Esophageal Squamous Cell Carcinoma

“…Therefore it is postulated that MMP-12 is perhaps is associated with tumor invasion and metastasis. In fact, Kachra et al [14]found that anaplastic astrocytomas and grade IV glioblastomas expressed significantly higher levels of MMP-12 than grade I meningiomas, and Kerkela et al [13]noted that both protein and mRNA of MMP-12 were expressed more in less differentiated SCC. In agreement with the results of Kerkela et al, we detected that esophageal SCCs which expressed high amounts of MMP-12 mRNA led to metastasis more easily than those without MMP-12 expression (p < 0.05).…”

“…In contrast, Kerkela et al [13]found that MMP-12 expression in skin cancer correlated with epithelial dedifferentiation and histologic aggressiveness. In human brain tumors, anaplastic astrocytomas and grade IV glioblastomas expressed significantly higher levels MMP-12 than grade I meningiomas [14]. Recently, Salmela et al [15]found esophageal adenocarcinoma expressed MMP-12 in tumor-infiltrating macrophages.…”