A Disintegrin and Metalloproteinase (ADAM) Family—Novel Biomarkers of Selected Gastrointestinal (GI) Malignancies?

Abstract

The global burden of gastrointestinal (GI) cancers is expected to increase. Therefore, it is vital that novel biomarkers useful for the early diagnosis of these malignancies are established. A growing body of data has linked secretion of proteolytic enzymes, such as metalloproteinases (MMPs), which destroy the extracellular matrix, to pathogenesis of GI tumours. A disintegrin and metalloproteinase (ADAM) proteins belong to the MMP family but have been proven to be unique due to both proteolytic and adhesive properties. Recent investigations have demonstrated that the expression of several ADAMs is upregulated in GI cancer cells. Thus, the objective of this review is to present current findings concerning the role of ADAMs in the pathogenesis of GI cancers, particularly their involvement in the development and progression of colorectal, pancreatic and gastric cancer. Furthermore, the prognostic significance of selected ADAMs in patients with GI tumours is also presented. It has been proven that ADAM8, 9, 10, 12, 15, 17 and 28 might stimulate the proliferation and invasion of GI malignancies and may be associated with unfavourable survival. In conclusion, this review confirms the role of selected ADAMs in the pathogenesis of the most common GI cancers and indicates their promising significance as potential prognostic biomarkers as well as therapeutic targets for GI malignancies. However, due to their non-specific nature, future research on ADAM biology should be performed to elucidate new strategies for the diagnosis of these common and deadly malignancies and treatment of patients with these diseases.