Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer

Abstract

The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a limited (n=33) number of patients. Broad-spectrum matrix metalloproteinase activity and both the active and latent forms of the gelatinases matrix metalloproteinase-2 and -9 were higher in tumour than in normal mucosa. The ratio's between active and latent forms of matrix metalloproteinase-2 and -9 were highest in tumour tissue and normal mucosa, respectively. Matrix metalloproteinase-2 levels, both active and latent forms, correlated inversely with stage of disease, the tumours without synchronous distant metastases containing significantly (P=0.005) more active matrix metalloproteinase-2 than the others. At much lower levels of activity, the same trend was observed in distant normal mucosa. The level of latent form of matrix metalloproteinase-9 in tumour depended on tumour location. Neither the active form of matrix metalloproteinase-9 nor broad-spectrum matrix metalloproteinase activity in tumour tissue did correlate with any of the clinicopathological parameters investigated. The results demonstrate explicit differences between the activity of matrix metalloproteinase-2 and -9, indicating different roles for both gelatinases in tumour progression. Such data are necessary in order to develop rational anti-cancer therapies based on inhibition of specific matrix metalloproteinases.

Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model

“…Moreover, recent evidence indicates that deregulation of MMP expression contributes to invasion, metastasis, and tumor angiogenesis (49 -55). For example, overexpression of MMP-2 and MMP-9 has been reported to be positively associated with the progression of human cancers (49)(50)(51)(52)(53)(54)(55)(56)(57)(58). Our present results suggest that I3C can inhibit metastasis of breast cancer cells mediated by the inhibition of MMP-9 expression.…”

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

“…Upregulation of MMP-2 is seen in solid tumours including hepatocellular (Maatta et al, 2000), colorectal (Liabakk et al, 1996;Baker et al, 2000;Waas et al, 2002) and ovarian cancers (Lengyel et al, 2001). With regard to the relation of MMP activity, as assessed by gelatin zymography, with prognosis, results differ between studies and tumour types.…”

“…Reports using semiquantitative gelatin zymography have correlated MMP-2 and/or MMP-9 activity with survival and disease progression in several solid tumour types (Brown et al,1993b;Tokuraku et al, 1995;Ikebe et al, 1999;Papathoma et al, 2000;Lengyel et al, 2001;Di Nezza et al, 2002;Waas et al, 2002). The use of SDS in the buffers activates latent gelatinase isoforms, which enables assessment of both the latent (pro) and active bands of enzymatic activity.…”

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

“…Varied expressions with increasing grade of dysplasia and inflammation have been observed (9,(17)(18)(19). In cancer immunology, a clear role of MMP7 and of other MMPs has been shown in tumour growth and invasion (17,(20)(21)(22)(23)(24)(25). Increased MMP7 expression in tumour tissue, serum, lymph nodes and peritoneal liquid generally correlates with worse prognosis, a tendency for metastatic disease and reduced overall survival (18,(26)(27)(28)(29)(30)(31)(32).…”

“…This was due to the fragility and poor staining of the specimens from such patients, whereby only five cases were accepted for examination. Given the role of MMP7 in abnormal tissue remodelling after RT injury (9,25,29) and its relation to progressive and metastatic colorectal disease, it may be rational to use potential preventive or therapeutic specific tissue inhibitors of MMPs with RT.…”