| Background |
α-2-Macroglobulin (A2M) is a conserved tetrameric pan protease inhibitor found in many biological fluids, including plasma and cerebral spinal fluid. A2M can bind to most proteases, as well as growth factors, hormones, and cytokines. Clearance of A2M-bound proteins is mediated by low-density lipoprotein receptor-related protein 1 (LRP1/CD91). Blood A2M levels decrease with age in humans, and this decrease may promote tumor development. In rodents, A2M modulates tumor cell adhesion, migration, and growth through inhibition of PI3K/Akt and SMAD pathways. Conversely, interaction with MMP2 may inhibit MMP2 activity in aged rat kidney, resulting in age-related accumulation of ECM and fibrosis. A2M may be a useful biomarker for liver fibrosis.
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