Current Perspectives on the Role of Matrix Metalloproteinases in the Pathogenesis of Basal Cell Carcinoma

Abstract

Basal cell carcinoma (BCC) is the most common skin malignancy, which rarely metastasizes but has a great ability to infiltrate and invade the surrounding tissues. One of the molecular players involved in the metastatic process are matrix metalloproteinases (MMPs). MMPs are enzymes that can degrade various components of the extracellular matrix. In the skin, the expression of MMPs is increased in response to various stimuli, including ultraviolet (UV) radiation, one of the main factors involved in the development of BCC. By modulating various processes that are linked to tumor growth, such as invasion and angiogenesis, MMPs have been associated with UV-related carcinogenesis. The sources of MMPs are multiple, as they can be released by both neoplastic and tumor microenvironment cells. Inhibiting the action of MMPs could be a useful therapeutic option in BCC management. In this review that reunites the latest advances in this domain, we discuss the role of MMPs in the pathogenesis and evolution of BCC, as molecules involved in tumor aggressiveness and risk of recurrence, in order to offer a fresh and updated perspective on this field.

Keywords: BCC; MMP; TIMP; invasion; tumor progression.

Figure 1

The interplay between MMPs and the tumor microenvironment. In the tumor microenvironment, MMPs are released by fibroblasts and immune cells, as well as by tumor cells. Plasminogen binds to its receptors and is converted to plasmin by urokinase plasminogen activator (uPA). In turn, plasmin may activate various MMPs and certain growth factors. All these molecules create a suitable microenvironment for ECM degradation, tumor cell invasion and migration.