Table 2.
Functional relationships between laminins and proteases in multiple epithelia*
| Laminin ligand/chain | Protease partner | Cleavage/Regulation | Animal/cell types | Biological effects | Refs |
|---|---|---|---|---|---|
| α1 (laminin111) | Elastase | Cleavage of laminin α1 by elastase | RAW264.7 macrophages | Enhances the production of uPA (urokinase type plasminogen activator) and MMP-9 | (113) |
| MMP-3 | Cleavage of laminn α1 by MMP-3 | MMP-3 knock-out mice | Cleavage of laminin by MMP-3 increases the blood-brain barrier permeability | (114) | |
| α3 (laminin332) | MMP-1, MMP-9 | Induction of MMPs by LG4 domain of laminin α3 | Keratinocytes | Enhances cell migration | (96,115) |
| α5 (laminin511) | MMP-9 | Induction of MMP-9 by peptide of laminin α5, NH2-AQARSAAKVKVSMKF-COOH | Macrophages | Induces inflammatory cell chemotaxis and metalloproteinase activity | (98) |
| MT1-MMP | Proteolytic cleavage of laminin α5 | DU-145 prostate cancer type | Reduces cell adhesion and enhances cell migration | (116) | |
| β3 (laminin332) | MT1-MMP | Proteolytic cleavage of laminin β3 to 80 kDa fragment | Prostate carcinoma cells | Enhances cell migration | (117) |
| γ1 (laminin111) | MMP-9 | Induction of MMP-9 by the peptide of laminin γ1, NH2-KAFDITYVRLKF-COOH | B16-F10 melanoma cells | Promotes pulmonary metastasis | (99) |
| γ2 (laminin332) | MT1-MMP | Proteolytic cleavage of laminin γ2 | MCF10A mammary epithelial cells | Enhances cell migration | (118) |
| MMP-2 | Proteolytic cleavage of laminin γ2 | Melanoma cells, Breast epithelial cell | Induces invasive and metastatic potential of melanoma cells, enhances cell migration | (119,120) | |
| MMP-19 | Proteolytic cleavage of laminin γ2 to 105 kDa and 80 kDa fragments | HaCaT keratinocytes | Enhances cell migration | (121) | |
| Laminin-332 | MMP-10 | Proteolytic cleavage of laminin γ2 | Keratinocytes | Disorganizes cell migration, increases apoptosis in damaged keratinocytes | (122) |
| MT1-MMP | Proteolytic cleavage of domain III of laminin γ2 | Human gastric carcinoma | Expression of MT1-MMP enhances the spreading of tumor via degradation of laminin | (97) | |
| MT1-MMP | Induction of MT1-MMP by laminin-332 | Thymocytes | Promotes mature thymocyte migration via laminin-332 and MT1-MMP | (123) | |
| Laminin | MMP-9 | Proteolytic cleavage of laminin | Neuronal cells | Induces neuronal apoptosis, causing stroke | (124) |
| Kallikerin 24 | Hydrolyze laminin | Leydig cells | n.k. | (125) |
n.k., effects not known; MMP, matrix metalloprotease; MT1-MMP, membrane-type 1-MMP, a membrane associated MMP that serves as a receptor for some MMPs (e.g., pro MMP-2) and their activation, also known as MMP-14.
*
Only selected references are given herein because this Table is not intended to be exhaustive. Our goal is to select recent findings in the field that specific cleavage of luminin chains by their protease partners can generate biologically active fragments to regulate a wide range of physiological functions (see text for details).