Faculty Opinions recommendation of Mechanisms of irregular bleeding with hormone therapy: the role of matrix metalloproteinases and their tissue inhibitors.

Abstract Context: Irregular bleeding is common in users of combined hormone therapy (HT) and often leads to invasive and expensive investigations to exclude underlying pathology. The mechanisms of HT-related bleeding are poorly understood. Endometrial matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to regulate bleeding during the normal menstrual cycle and are known to be altered in breakthrough bleeding with progestogen-only contraception. Objective: The aim of this study was to determine how HT exposure alters endometrial production of MMP-1, -3, -9, and -14 and their tissue inhibitors TIMP-1, -2, -3, and -4 and to determine the relationship between MMP and TIMP production and bleeding patterns in HT users. Endometrial leukocytes regulating MMP production and activation were also assessed. Design: A prospective observational study was conducted between 2003 and 2005. Setting and Patients: The study occurred at a tertiary referral menopause clinic at King Edward Memorial Hospital, Western Australia, and included 25 postmenopausal women not taking HT and 73 women taking combined HT. Interventions: Endometrium was obtained during and outside bleeding episodes. Main Outcome Measures: We assessed production of MMP-1, -3, -9, and -14 and their tissue inhibitors TIMP-1, -2, -3, and -4 and their relationship to bleeding patterns in HT users. Results: All MMPs studied, with the exception of MMP-9, were expressed at low levels in postmenopausal endometrium. Increases in both MMP-3 and -9 localization were seen in association with irregular bleeding, but these did not reach statistical significance. Endometrial production of TIMP-1 was significantly increased in association with bleeding. Endometrial leukocytes were not related to bleeding, with the exception of uterine natural killer cells, which were significantly increased during bleeding, as previously published. Conclusions: Irregular bleeding in HT users is associated with a distinct pattern of MMP and TIMP production that differs from that seen in normal menstrual bleeding and from that seen in contraceptive-related breakthrough bleeding. This suggests that the endometrial balance between MMP and TIMP contributes to vascular breakdown with HT but by a different mechanism than that seen in normal menstruation or in breakthrough bleeding.

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The Role of Polymorphic Variants of Several Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Development of Gastric Cancer

Russian Journal of Genetics ◽

10.1134/s1022795421050021 ◽

2021 ◽

Vol 57 (5) ◽

pp. 607-619

Author(s):

L. F. Gallyamova ◽

A. Kh. Nurgalieva ◽

I. I. Khidiyatov ◽

T. R. Nasibullin ◽

F. R. Munasypov ◽

...

Keyword(s):

Gastric Cancer ◽

Matrix Metalloproteinases ◽

Tissue Inhibitors ◽

Polymorphic Variants ◽

Development Of Gastric Cancer

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MP19-18 THE ROLE OF MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS IN THE OBSTRUCTED BLADDER SECONDARY TO BENIGN PROSTATIC HYPERPLASIA: ANALYSIS OF EXPRESSION OF 8 GENES

The Journal of Urology ◽

10.1016/j.juro.2014.02.719 ◽

2014 ◽

Vol 191 (4S) ◽

Author(s):

Yuri A. Ferreira ◽

Joao A. Barbosa ◽

Marco A. Nunes ◽

Sabrina T. Reis ◽

Nayara I. Viana ◽

...

Keyword(s):

Benign Prostatic Hyperplasia ◽

Matrix Metalloproteinases ◽

Prostatic Hyperplasia ◽

Tissue Inhibitors

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The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Duchenne Muscular Dystrophy Cardiomyopathy

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2019.02.006 ◽

2019 ◽

Vol 25 (4) ◽

pp. 259-267 ◽

Cited By ~ 6

Author(s):

Jonathan H, Soslow ◽

Meng Xu ◽

James C. Slaughter ◽

Kimberly Crum ◽

Joshua D. Chew ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Matrix Metalloproteinases ◽

Tissue Inhibitors Of Metalloproteinases ◽

Tissue Inhibitors ◽

Duchenne Muscular Dystrophy Cardiomyopathy

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Functional Analysis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Differentially Expressed by Variants of Human HT-1080 Fibrosarcoma Exhibiting High and Low Levels of Intravasation and Metastasis

Journal of Biological Chemistry ◽

10.1074/jbc.m705993200 ◽

2007 ◽

Vol 282 (49) ◽

pp. 35964-35977 ◽

Cited By ~ 25

Author(s):

Juneth J. Partridge ◽

Mark A. Madsen ◽

Veronica C. Ardi ◽

Thales Papagiannakopoulos ◽

Tatyana A. Kupriyanova ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Cancer Cell ◽

Small Interfering Rna ◽

Cultured Cells ◽

Tissue Inhibitors Of Metalloproteinases ◽

Down Regulation ◽

Primary Tumors ◽

Tissue Inhibitors ◽

Interfering Rna

The role of tumor-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in cancer cell dissemination was analyzed by employing two variants of human HT-1080 fibrosarcoma, HT-hi/diss and HT-lo/diss, which differ by 50-100-fold in their ability to intravasate and metastasize in the chick embryo. HT-hi/diss and HT-lo/diss were compared by quantitative reverse transcription-PCR and Western blot analyses for mRNA and protein expression of nine MMPs (MMP-1, -2, -3, -7, -8, -9, -10, -13, and -14) and three TIMPs (TIMP-1, -2, and -3) in cultured cells in vitro and in primary tumors in vivo. MMP-1 and MMP-9 were more abundant in the HT-hi/diss variant, both in cultures and in tumors, whereas the HT-lo/diss variant consistently expressed higher levels of MMP-2, TIMP-1, and TIMP-2. Small interfering RNA-mediated down-regulation of MMP-2 and TIMP-2 increased intravasation of HT-lo/diss cells. Coordinately, treatment of the developing HT-hi/diss tumors with recombinant TIMP-1 and TIMP-2 significantly reduced HT-hi/diss cell intravasation. However, a substantial increase of HT-hi/diss dissemination was observed upon small interfering RNA-mediated down-regulation of three secreted MMPs, including the interstitial collagenase MMP-1 and the two gelatinases, MMP-2 and MMP-9, but not the membrane-tethered MMP-14. The addition of recombinant pro-MMP-9 protein to the HT-hi/diss tumors reversed the increased intravasation of HT-hi/diss cells, in which MMP-9 was stably down-regulated by short hairpin RNA interference. This rescue did not occur if the pro-MMP-9 was stoichiometrically complexed with TIMP-1, pointing to a direct role of the MMP-9 enzyme in regulation of HT-hi/diss intravasation. Collectively, these findings demonstrate that tumor-derived MMPs may have protective functions in cancer cell intravasation, i.e. not promoting but rather catalytically interfering with the early stages of cancer dissemination.

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