Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.23 (
MMP
)
4,246
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Approximately 4,000 babies with nonsyndromic cleft lip with or without cleft palate (NSCLP) are born each year in the United States. Because NSCLP exhibits both etiologic and genetic heterogeneity, attempts to identify the underlying genetic causes have met with limited success and the pursuit of early promising findings have yielded mixed results. Two recent genomic scans identified a number of suggestive regions; some of these results have been supported by our lab and others in subsequent studies. Using our NSCLP multiplex family population, we were able to provide additional supportive evidence for association to the regions 2q37, 11p12-14, 12q13, and 16p13.11-p12 that were identified in the genomic scans. However, there remains a number of additional viable candidate genes and regions that have not been sufficiently investigated. These include chromosomal translocations in patients with NSCLP, growth factor genes, metalloproteinase (
MMP
) and transcription factor (patterning) genes, including those in the WNT family. Here, we present results from screening the 10p13 chromosomal translocation region associated with NSCLP,
MMP
genes clustered on chromosomes 1p36, 11q22.3, 16p13.3, and 16q12-13, and the region containing the WNT5A gene on chromosome 3p21. Markers from three of the regions, 10p13, 16p13.3 (
MMP25
), and 3p21.2, yielded findings that are sufficiently significant to warrant closer investigation.
...
PMID:Association of chromosomal regions 3p21.2, 10p13, and 16p13.3 with nonsyndromic cleft lip and palate. 1475 62
Tumor-cell infiltration is a major obstacle to successful therapy for brain tumors. Membrane-type matrix metalloproteinases (MT-MMPs), a metzincin subfamily of six proteases, are important mediators of infiltration. The cellular source of MT-MMPs and their role in glioma biology, however, remain controversial. Thus, we comprehensively analyzed the expression of MT-MMPs in primary brain tumors. All MT-MMPs were differentially expressed in primary brain tumors. In diffuse gliomas, MT-MMP1, -3, and -4 were predominantly expressed by IDH1
mutated
tumor cells, while macrophages/microglia contributed significantly less to MT-
MMP
expression. For functional analyses, individual MT-MMPs were expressed in primary mouse p53
-/-
astrocytes. Invasion and migration potential of MT-
MMP
-transduced astrocytes was determined via scratch, matrigel invasion, and novel organotypic porcine spinal slice migration (OPoSSM) and invasion assays. Overall, MT-
MMP
-transduced astrocytes showed enhanced migration compared to controls. MMP14 was the strongest mediator of migration in scratch assays. However, in the OPoSSM assays, the glycosylphosphatidylinositol (GPI)-anchored MT-MMPs MMP17 and
MMP25
, not MMP14, mediated the highest infiltration rates of astrocytes. Our data unequivocally demonstrate for the first time that glioma cells, not microglia, are the predominant producers of MT-MMPs in glioma and can act as potent mediators of tumor-cell infiltration into CNS tissue. These proteases are therefore promising targets for therapeutic interventions.
...
PMID:Neoplastic Cells are the Major Source of MT-MMPs in
IDH1
-Mutant Glioma, Thus Enhancing Tumor-Cell Intrinsic Brain Infiltration. 3287 36
