MMP24

MMP24

A gene on chromosome 20q11.2 that encodes membrane-type matrix metalloproteinase 24. Unlike other matrix metalloproteinases, which are secreted as inactive proproteins and activated when cleaved by extracellular proteinases, MMP24 is a transmembrane protein. It activates progelatinase A and may also cleave proteoglycans (e.g., dermatan and chondroitin sulfates) and partially cleave fibronectin.
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Of the other four MMPs expressed at moderate levels in hMSCs at day 0 (MMP14, MMP16, MMP19, and MMP24), only MMP14 can degrade collagen type I, FN, and LN [30-32].
Membrane type MMPs (MT-MMP) (MMP-14, MMP-15, MMP-16, MMP-17, MMP24, and MMP-25) are anchored to the plasma membrane by a transmembrane domain with a cytoplasmic domain or a glycosylphosphatidylinositol (GPI).
Due to structural and substrate specificity, MMPs are currently divided into seven classes: collagenases (MMP1, MMP8, MMP13, and MMP18), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP10), stromelysin like (MMP11 and MMP12), matrilysins (MMP7 and MMP26), membrane type (MMP14, MMP15, MMP16, MMP17, MMP24, and MMP25), and others (MMP19, MMP20, MMP21, MMP22, MMP23, MMP27, and MMP28) [18, 27, 28].
Primers and probes were designed and validated by Applied Biosystems for 18SRNA (4308329), MMP1 (Hs00899658_m1), MMP2 (Hs00234422_m1), MMP3 (Hs00968308_m1), MMP8 (Hs01029057_m1), MMP9 (Hs00234579_m1), MMP13 (Hs00233992_m1), MMP14 (Hs00237119_m1), MMP16 (Hs00254755_m1) MMP24 (Hs00198580_m1), MMP25 (Hs01554789_m1), TIMP1 (Hs99999139_m1), and TIMP3 (Hs00165949_m1).
In SG, levels of MMP24 could vary since in 11/22 samples expression was not detected, while the rest of the samples presented low (8/22) and moderate expression (3/22); likewise, in GC, MMP24 was expressed at moderate (8/17), low (8/17), and not detected (1/17) levels.
In addition, no correlations were detected between gene expression of MMP1, MMP2, MMP3, MMP8, MMP9, MMP13, MMP14, MMP16, MMP24, MMP25, TIMP1 and TIMP3 and the variables of age, gender, size and degree of differentiation (P > 0.05).
This study showed the existence of differences in the expression of MMP2, MMP24, and MMP25 between GC and SG, with expression significantly higher in GC compared to SG.
In addition, there is no correlation or association between the expression of the genes (MMP1, MMP2, MMP3, MMP8, MMP9, MMP13, MMP14, MMP16, MMP24, MMP25, TIMP1, and TIMP3) and proteins (MMP-2 zymogen, MMP-2 active form, the catalytic domain of MMP-2 [33], MMP-3, MMP9/lipocalin, MMP-9 zymogen, MMP-9 active form, TIMP1/MMP-1, TIMP-1 monomer, TIMP-3 dimer, and TIMP-3 monomer) and the variables of age, gender, size, and degree of differentiation.
In conclusion, this study represents the first partial pattern of gene expression of MMPs and TIMPs in GC and SG conducted in Mexican population and shows that the mRNA levels of MMP2 are significantly higher in advanced GC compared to SG; interestingly, levels of MMP24 and MMP25 are also elevated in GC compared to SG.
Membrane-anchored MMPs include MT1-MMP (MMP14), MT2-MMP (MMP15), MT3-MMP (MMP16), MT4-MMP (MMP17), MT5-MMP (MMP24), MT6-MMP (MMP25), and MMP23.