MMP9
MMP9 (matrix metalloproteinase 9, gelatinase B) is a secreted enzyme that degrades collagen IV and gelatin, the structural components of basement membranes.
Function
MMP9 is secreted as a zymogen by neutrophils, macrophages, and stromal cells and activated by proteolytic cleavage at the membrane or in the extracellular space. Its substrates are basement-membrane collagens and denatured collagen (gelatin), so its physiological roles involve breaking through barriers: wound healing, bone remodeling, immune-cell diapedesis, and endometrial cycling. The enzyme is regulated at three levels - transcription (induced by inflammatory cytokines such as TNF and IL-6), zymogen activation, and inhibition by TIMP tissue inhibitors - and its activity therefore reflects the balance between inflammatory demand and tissue integrity.
In cancer
Tumors recruit MMP9 from stromal cells and neutrophils more than they produce it themselves. The enzyme clears basement membrane for invasion, releases matrix-bound growth factors (VEGF among them), and generates collagen fragments that promote angiogenesis and motility. MMP9 expression correlates with metastasis across tumor types. The broad-spectrum MMP inhibitor trials of the 1990s failed - wrong substrates, wrong stage of disease - and the lesson they left is that matrix proteolysis works as a system, with redundancy among family members.
Notes
- Human gene symbol: MMP9; UniProt P14780; 707 amino acids; gelatinase subfamily, three fibronectin type II repeats.