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Table 1 This table shows the degradation of collagenous and non-collagenous substrates by important MMPs

From: The anti-neoplastic effect of doxycycline in osteosarcoma as a metalloproteinase (MMP) inhibitor: a systematic review

Metalloproteinase (MMP)MMP-substratesOsteosarcoma experimental trialMetastatic action
MMP-1 (collagenase-1)Collagen (I, II, III, VII, VIII, X), casein, entactin, laminin, pro-MMP-1, -2, -9, and serpinIntratibial 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, fibronectin1. MNNG/HOS cells in NOD/SCID/IL2rγnull mice treated with N-α-Acetyltransferase [9]↑ MMP-2
2. Intratibial injection of MNNG/HOS cells in SCID mice treated with resveratrol [10]↓ microRNA-328
↓ metastases
MMP-3 (stromelysin-1)Laminin, aggrecan, gelatin, fibronectinMMP-3 knockdown in MG-63 and TE85 osteosarcoma cells [13]↓MMP-3
MMP-9 (gelatinase B)Gelatin, collagens (IV, V, VII, X, XIV), elastin, fibrillin, osteonectinControl or HEY1 shRNA-transfected 143B cells inoculated in knee joint of nude mice [14]↑HEY1
MMP-11 (stromelysin-3)Fibronectin, laminin, aggrecan, gelatinHuman osteosarcoma cell lines (HOS, Saos-2, MG-63 and U2OS) with downregulation of miR‑125a‑5p [18]↓miR‑125a‑5p
MMP-13 (collagenase-3)Collagen (II, III, IV, IX, X), proteoglycans, fibronectin, laminin, elastin1.Athymic nude mice inoculated with 143B cells in knee treated with or without miR‐143(targets plasminogen activator inhibitor-1) [19]↑ miR‐143
2. Knockdown of IL-32 in MG-63 osteosarcoma cells [20]↓IL-32
  1. In vitro and in vivo osteosarcoma trials have indicated the key role of these MMPs in tumor metastasis [21]