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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-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

  1. In vitro and in vivo osteosarcoma trials have indicated the key role of these MMPs in tumor metastasis [21]