Metalloproteinase (MMP) | MMP-substrates | Osteosarcoma experimental trial | Metastatic action |
---|---|---|---|
MMP-1 (collagenase-1) | Collagen (I, II, III, VII, VIII, X), casein, entactin, laminin, pro-MMP-1, -2, -9, and serpin | Intratibial injection of 143B cells with shRNA-downregulated MMP-1 expression in SCID mice [8] | ↓lung micro- and macro-metastases than control-group |
MMP-2 (gelatinase A) | Gelatin, collagen (IV–VI, X), elastin, fibronectin | 1. MNNG/HOS cells in NOD/SCID/IL2rγnull mice treated with N-α-Acetyltransferase [9] | ↑ MMP-2 ↑metastases |
2. Intratibial injection of MNNG/HOS cells in SCID mice treated with resveratrol [10] | ↓ microRNA-328 ↓MMP-2 ↓ metastases | ||
MMP-3 (stromelysin-1) | Laminin, aggrecan, gelatin, fibronectin | MMP-3 knockdown in MG-63 and TE85 osteosarcoma cells [13] | ↓MMP-3 ↓metastases |
MMP-9 (gelatinase B) | Gelatin, collagens (IV, V, VII, X, XIV), elastin, fibrillin, osteonectin | Control or HEY1 shRNA-transfected 143B cells inoculated in knee joint of nude mice [14] | ↑HEY1 ↑MMP-9 ↑metastases |
MMP-11 (stromelysin-3) | Fibronectin, laminin, aggrecan, gelatin | Human osteosarcoma cell lines (HOS, Saos-2, MG-63 and U2OS) with downregulation of miR‑125a‑5p [18] | ↓miR‑125a‑5p ↑MMP-11 ↑metastases |
MMP-13 (collagenase-3) | Collagen (II, III, IV, IX, X), proteoglycans, fibronectin, laminin, elastin | 1.Athymic nude mice inoculated with 143B cells in knee treated with or without miR‐143(targets plasminogen activator inhibitor-1) [19] | ↑ miR‐143 ↓MMP-13 ↓metastases |
2. Knockdown of IL-32 in MG-63 osteosarcoma cells [20] | ↓IL-32 ↓MMP-13 ↓invasiveness |