Disease relevance of Mmp11

• Adipocyte hypertrophy in stromelysin-3 deficient mice with nutritionally induced obesity [1].
• At the time of sacrifice, the body weight of the MMP-11-/- mice was higher than that of the MMP-11+/+ mice (36+/-1.4 g versus 29+/-0.9 g, p = 0.0002) [1].
• In addition, tumors obtained after sub-cutaneous injection of ST3-expressing or nonexpressing cells did not exhibit obvious histological differences, and careful examination did not reveal any local invasive tissue areas nor systemic metastases [2].
• Stromelysin-3 (ST3) is a matrix metalloproteinase expressed in human carcinomas in ways suggesting that it may play a role in tumor progression [2].
• Since the ST3 gene is also specifically expressed in fibroblastic cells surrounding invasive neoplastic cells of breast carcinomas, we suggest that ST3 is implicated in extracellular matrix remodeling processes common to mammary apoptosis and breast cancer progression [3].

High impact information on Mmp11

• In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-gamma, or tumor necrosis factor alpha did not augment stromelysin-3 in vascular wall cells [4].
• Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion [4].
• In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma [4].
• T-T tumor hybrids were constructed between the AKR SL3 thymoma and an H-2-distinguishable thymoma cell line [5].
• To test this possibility, we have performed gene transfer experiments using both anti-sense and sense ST3 expression vectors, and malignant cells either expressing (NIH 3T3 fibroblasts) or not (MCF7 epithelial cells) endogenous ST3 [2].

Chemical compound and disease context of Mmp11

• The four different strains of human rotavirus (Wa, KUN, MO, and ST3) were inactivated in vitro by treatment with PSK, a protein-bound polysaccharide preparation, in a dose-dependent manner [6].

Biological context of Mmp11

• Via Northern and in situ hybridization, we have analyzed the spatio-temporal expression patterns of members of the MMP family (stromelysin-3, gelatinases A and B), as well as their inhibitors TIMP-1, -2 and -3 in late murine placenta (days 10.5 to 18.5 of gestation) [7].
• Altogether, these results indicate that ST3 expression promotes tumor take in nude mice, presumably by favoring cancer cell survival in a tissue environment initially not permissive for tumor growth [2].
• The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis [3].
• The ST3 protein is well conserved between humans and mice, and the pattern of ST3 gene expression is similar in both species, and shows expression in the placenta, in the uterus, and during limb bud morphogenesis [3].
• In this study we report the ST3 gene inactivation by homologous recombination [8].

Anatomical context of Mmp11

• Adipocytes in MMP-11-/- adipose tissue were hypertrophic as compared to MMP-11+/+ adipocytes (volume of 57+/-12 x 10(3) microm3 versus 31+/-2.4 x 10(3) microm3 for SC fat, and 100+/-18 x 10(3) microm3 versus 57+/-7.6 x 10(3) microm3 for GON fat; both p < 0.06) [1].
• The areas of stromelysin-3 expression were the same (giant trophoblasts) or adjacent (decidua) to those where urokinase (uPA) transcripts were detected, suggesting a possible cooperation between these proteinases in placental remodeling [7].
• However, once established, the ST3 expressing tumors did not grow faster than those obtained with the parental MCF7 cell line [2].
• 3T3 cells expressing anti-sense ST3 RNA showed reduced tumorigenicity, and MCF7 cells expressing mouse or human ST3 were associated with reduced tumor-free period leading to a significant increased tumor incidence(P<10(-4)) [2].
• We show that the ST3 gene can also be expressed in the normal mouse mammary gland [3].

Associations of Mmp11 with chemical compounds

• One ST3 inhibitor belonging to the cephalosporin family of antibiotics was thereby identified [9].
• Among the RAREs, the proximal DR1-RARE was shown to be sufficient for ST3 promoter activation by ligand-bound retinoid receptors, whereas the two distal DR2-RAREs appear to be involved more in the control of base-line promoter activity [10].
• Our findings therefore assign to C/EBP, retinoids, and thyroid hormone important roles in the regulation of ST3 gene expression [10].
• Accordingly, ST3 expression was induced by retinoic acid and was reduced in cells where specific retinoic acid receptors had been inactivated [10].
• Role of the S1' subsite glutamine 215 in activity and specificity of stromelysin-3 by site-directed mutagenesis [11].

Regulatory relationships of Mmp11

• Importantly, TGFbeta induces stromelysin-3 in fibroblasts by similar mechanisms, indicating that it is likely to stimulate stromelysin-3 expression in breast stroma [12].
• Deglycosylation of CD147 down-regulates Matrix Metalloproteinase-11 expression and the adhesive capability of murine hepatocarcinoma cell HcaF in vitro [13].

Other interactions of Mmp11

• Several matrix metalloproteinases (MMPs), including the stromelysins MMP-3 and MMP-11, are expressed in adipose tissue [1].
• Using an RNA interference (RNAi) strategy, we showed that the down-regulation of Cav-1 in Hca-F/RNAi cells could suppress the conversion of LG-CD147 to HG-CD147, down-regulate MMP-11 expression and decrease Hca-F/RNAi cell invasion [14].
• By partial analogy with interstitial collagenase, one hypothesis is that stromelysin-3 with an intact C-terminal domain has specific properties for an as yet undefined substrate [15].
• The matrix-degrading metalloproteinases stromelysin-1, stromelysin-3, and gelatinase A are expressed during ductal branching morphogenesis of the murine mammary gland [16].
• Overexpression of PACE4 led to a significant increase in the processing of stromelysin-3, a well-characterized substrate of this PC [17].

Analytical, diagnostic and therapeutic context of Mmp11

• Using mouse syngeneic model, light and electron microscopy showed that in ST3-deficient mice but not in wild-type mice, forced cancer cell-adipocyte interaction/crosstalk results in adipocyte membrane alteration, allowing cancer cell fat infiltration and death [18].
• We have used northern blot analysis and in situ hybridization to study the spatial distribution of stromelysin-3 (ST3) expression during mouse embryogenesis [19].
• To define critical structural determinants involved in controlling stromelysin-3 proteolytic activity, we have used site-directed mutagenesis [20].
• N-terminal sequencing and immunoblotting analysis with antibodies specific to distinct domains of stromelysin-3 indicated that the 27-28-Da stromelysin-3 forms had lost the predicted propeptide and the majority of the C-terminal domain [15].
• Molecular cloning and partial characterization of medaka fish stromelysin-3 and its restricted expression in the oocytes of small growing follicles of the ovary [21].

References