Production onf matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study

Abstract

Background. Matrix metalloproteinases (MMP) are a gene family of zinc enzymes capable of degrading almost all of the extracellular matrix macromolecules in vivo. Their enzymic activities are believed to be responsible for tumor invasion and metastasis. Methods. In this study, using peroxidase‐antiperoxidase method, monospecific antisera against MMP‐1 (tissue collagenase), MMP‐2 (type IV collagenase/72‐kilo‐dalton [KD] gelatinase), and MMP‐3 (stromelysin) were applied to 29 squamous cell carcinomas and normal epithelium of the esophagus to identify cells synthesizing and secreting these enzymes. Results. Immunoreactivity of MMP‐1, −2, and −3 was observed in small cancer nests of the deeply invasive or marginal portion of the tumor. Among the 29 patients studied, the presence of at least one MMP was observed in 17 (58.6%). All three enzymes were observed in six (20.6%) patients, MMP‐2 and −3 in five (17.2%) patients, only MMP‐2 in three (10.3%) patients, and MMP‐3 alone in three (10.3%) patients. There was a good correlation among histologic stage and tumor invasion, lymph node metastasis, and MMP expression. In particular, expression of MMP‐2 and −3 was closely related to lymph node metastasis and vascular invasion. Conclusions. These results suggest that MMP, especially MMP‐2 and −3, play an important role in tumor invasion and metastasis and that analysis of MMP‐2 and −3 production is useful for evaluation of malignant potential in esophageal carcinoma. Cancer 1992; 702747–53.

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma

“…Intriguingly, both MMPs were more highly expressed in the metastatic regions than in the primary regions of OSCC, and this pattern was quite prominent in gingival cancers. The increased expression of MMPs correlates with the proliferation and invasion of tumor cells (16)(17)(18)(19)(20)(21)(22)(23). The enhancement of MMP activity in cultured cells indicates increased metastatic potential (24)(25)(26).…”

Relationships Between Clinical Behavior of Laryngeal Squamous Cell Carcinomas and Expression of VEGF, MMP-9 and E-Cadherin

“…The progression and invasion capacity of tumor is associated to with the degradations of basement membrane (which is formed by Type IV collagen), and the fibrous capsule (which is formed by Type I and Type III collagen). Due to the proteolytic activity of MMP-9 enzyme that degrades type IV collagen, it increases tumor invasion and progression (Shima et al, 1992;Kusukawa et al, 1993;Sato et al, 1999) Hong et al (2000) found the significant relationship between MMP-9 expression and cervical metastatic disease. The increased expression of MMP-9 in patients with oral squamous cell carcinoma was stated as 73.7% in contrast with our study, and any correlation with decrease in histological differentiation has not been established.…”

Expression of vascular endothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in oesophageal cancer

“…Shima et al (1992) classified the stains of MMPs in oesophageal cancer into three groups. We, however, classified MMP-9 staining into two groups to simplify the data: negative, when the intensity of stain in cancer cells was negative or weaker than normal oesophageal epithelia; positive, when the intensity of staining was equal to or stronger than normal epithelia.…”

“…We previously reported that the expression of vascular endothelial growth factor (VEGF) is associated with lymph node metastasis and prognosis in oesophageal cancer (Uchida et al, 1998). Other reports showed that the expression of matrix metalloproteinases (MMPs) (Shima et al, 1992), E-cadherin (Kadowaki et al, 1994;Nakanishi et al, 1997) and p53 (Wang et al, 1994) in primary tumours correlated with lymph node metastasis of oesophageal cancer.…”