Journal article
Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines
Clinical cancer research, v 9(3), pp 1191-1199
01 Mar 2003
PMID: 12631625
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Insulin-like growth factor (IGF) I has been shown previously to up-regulate matrix metalloproteinase-2 (MMP-2) production, whereas the interleukin (IL) 10/IL-10 receptor axis has been found to down-regulate MMP-2 synthesis in tumor cells. In this paper, we showed that IL-10 activation of the IL-10 receptor blocked MMP-2 and membrane type 1 (MT1) -MMP transcription and protein synthesis in nonimmortalized primary human prostate cell strains (i.e., HPCA-10a and HPCA-10c) derived from high-grade cancer. Northern blots, Western blots, and ELISAs showed that IL-10 suppressed IGF-I induction of MMP-2 and MT1-MMP mRNA synthesis in these cell strains (P < 0.001). Inhibition studies with IL-10 and IGF-I receptor antibodies plus transfections experiments with IL-10 sense, and IGF-I receptor antisense constructs confirmed these results. Finally, transient transfection experiments and chloramphenicol acetyltransferase assays with different regions of the 5' promoter region of the MMP-2 gene (-1659 to -555 bp) additionally showed that IGF-I stimulated p53-dependent plasmid catecholamine acetyltransferase activity and that IL-10 blocked IGF-I-induced plasmid catecholamine acetyltransferase activity. Electrophoretic mobility shift assays revealed that IL-10 induced protein(s) binding to a putative "silencer element" (-1309 to -555 fragment) downstream of the p53 binding site (-1649 to -1640). The data show that IL-10 blocks IGF-I activation of MMP-2 and MT1-MMP mRNA expression and protein synthesis in primary prostate cell strains.
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Details
- Title
- Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines
- Creators
- Mark E StearnsMin WangYouji HuFernando U GarciaJohng Rhim
- Publication Details
- Clinical cancer research, v 9(3), pp 1191-1199
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Decision Sciences (and Management Information Systems); Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000181430400038
- Scopus ID
- 2-s2.0-0037339755
- Other Identifier
- 991019167841504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology