Moving targets: Emerging roles for MMPs in cancer progression and metastasis

Abstract

Matrix metalloproteinases have long been associated with cancer. Clinical trials of small molecule inhibitors for this family of enzymes however, were spectacularly unsuccessful in a variety of tumor types. Here, we discuss some of the newer roles that have been uncovered for MMPs in cancer that would not have been targeted with those initial inhibitors or in the patient populations analyzed. We also consider novel ways of using cancer-associated MMP activity for clinical benefit.

Keywords: Activity-based probe; Efficacy; Imaging; Non-catalytic; Pre-metastatic niche; Theranostic; Therapy.

Figure 1. MMPs in pre-metastatic niche development

Primary tumor derived exosomes, containing MMPs, are released into the circulation (1). Exosomes interact with resident cells in the pre-metastatic tissue (2). Exosome and pre-metastatic niche derived MMPs can modulate ECM components and factors such as chemokines that in turn are systemically released (3). In response, bone marrow derived cells (BMDCs) are mobilized and recruited to the developing pre-metastatic niche where they create a favorable environment for metastatic cells in part, via the secretion of MMPs (4).