Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets

Abstract

Biomarkers are used as tools in cancer diagnostics and in treatment stratification. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs). This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. It has therefore been expected that MMPs could serve as both diagnostic and prognostic markers in cancer patients, but despite a huge number of studies, it has been difficult to establish MMPs as cancer biomarkers. In the present paper, we assess some of the challenges associated with MMP research as well as putative reasons for the conflicting data on the value of these enzymes as diagnostic and prognostic markers in cancer patients. We also review the prognostic value of a number of MMPs in patients with lung, colorectal, breast, and prostate cancers. The review also discusses MMPs as potential target molecules for therapeutic agents and new strategies for development of such drugs.

Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa) Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

“…Other matrix metalloproteinases, such as MMP-1 and MMP-7, similarly to MMP-9 exhibit proteolytic activity towards ECM, and these two enzymes also correlate with an aggressive phenotype of colorectal cancer [Hadler-Olsen et al, 2013]. Our study is the fi rst report on the inhibition of MMP-1 expression by the evening primrose polyphenol extract in a colon cancer cell line.…”

“…Except for neutrophils, cells do not accumulate MMPs. After synthesis, MMPs are secreted into the ECM as a latent form that can be activated by either proteolytic cleavage or by conformational changes induced, among others, by reactive oxygen species (ROS) [Hadler-Olsen et al, 2013].…”

PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells migration, proliferation and MMP-2/−9 expression

“…PT93 was reported as a selective MMP inhibitor, inhibiting MMP-2 and MMP-9 (22). A number of studies demonstrated that MMPs are associated with the ability of tumors to migrate and invade (12,26,27). First generation MMPIs with broad-spectrum MMP inhibitory ability cause unexpected side effects, including musculoskeletal pain and inflammation (12,15,16).…”

“…Higher levels of MMP-2 and MMP-9 were observed in high-grade gliomas compared with non-invasive low-grade astrocytoma and normal brain tissue (4,10). In the 1990s, following the identification of the important role of MMPs in cancer angiogenesis, growth and metastasis, MMPs became a therapeutic target for cancer treatment, which determined interest in the design and evaluation of matrix metalloproteinases inhibitors (MMPIs) as anticancer agents (11,12). MMPs have been revealed to be important in regulating cellular activities and are involved in physiological and pathological processes (13,14).…”

“…MMPs have been revealed to be important in regulating cellular activities and are involved in physiological and pathological processes (13,14). The first generation of MMPIs, which had broad-spectrum MMP inhibition activity, caused unexpected side effects, including musculoskeletal pain and inflammation (12,15,16).…”