Evaluation of heparanase and matrix metalloproteinase‐9 in patients with cutaneous malignant melanoma

Abstract

Elevated heparanase and matrix metalloproteinase (MMP)-9, frequently found in human cancer, is a major cause of degradation of the extracellular matrix (ECM) and basement membrane (BM), thus facilitating tumor cell migration and invasion. Although a lot of work has been done, the role of heparanase and MMP-9 has not been delineated in skin cancer progression. The purpose of this study was to do such an exploration. To investigate the role of heparanase and MMP-9 in cutaneous malignant melanoma (CMM) development, we performed immunohistochemical analysis to detect the alternation of these two factors in paraffin-embedded biopsy specimens of normal skin, junctional nevi and CMM. It is interesting to note that the expression profile of heparanase and MMP-9 was similar. Contrary to negative staining in normal skin, overexpression of heparanase and cytoplasmic MMP-9 was observed in as many as 70% of CMM, whereas only 10% of the junctional nevi exhibited faint staining (P = 0.0005, P = 0.0000). Considering the lymph node (LN) metastasis, the expression of the two factors is significantly higher in LN-positive lesions than that in LN-negative lesions (P = 0.0295, P = 0.0013). Meanwhile, there was positive correlation between the expression of MMP-9 and heparanase (r = 0.689, P = 0.003). The first expression of MMP-9 and heparanase occurs at benign lesions. However, the significantly increased expression in advanced CMM stages, particularly in LN-positive metastasis lesions, might synergistically contribute to degradation of ECM and BM, therefore promoting carcinogenesis and metastasis.

A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies

“…Monoclonal antibodies against MMP-2 and MMP-9 were also included in this experiment because both have a role in melanoma development [27], [28].…”

Irradiated Riboflavin Diminishes the Aggressiveness of Melanoma In Vitro and In Vivo

“…To study the effects of new antitumoral agents, many biomarkers have been investigated including matrix metalloproteinases (MMPs) which are regulated by their tissue inhibitors (TIMP). Chen and colleagues [56] analyzed samples from patients and reported that there is a differential expression of MMP-9, which is present in early stage of benign lesions and a significant increase occurs in advanced malignant melanoma stages. This variation in MMP-9 activity might contribute to degradation of extracellular matrix, thereby promoting carcinogenesis and metastasis.…”

Progression of cutaneous melanoma: implications for treatment

“…Furthermore, a recent study has shown marked increase in MMP-9 and Heparanase in cutaneous melanoma cells, especially ones that have metastasized to regional lymph nodes, as compared to tumors with negative SLN [24]. In another study, it has been clearly shown that MDA-9/Syntenin has a critical role with regard to melanoma metastasis.…”