Matrix Metalloproteinases and Their Inhibitors in Gestational Trophoblastic Diseases and Normal Placenta

Végh, György; Tuncer, Z S; Fülöp, Vilmos; Genest, David R.; Mok, Samuel C.; Berkowitz, Ross S.

doi:10.1006/gyno.1999.5564

Cited by 49 publications

(26 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to other human cancers, neoplastic transformation of trophoblast is likely to be a multistep process and involves multiple genetic alterations including activation of oncogenes and inactivation of tumor suppressor genes. 3,4 Potential biological markers related to malignant transformation of trophoblast include c-erbB-2, 5 cyclin E, 6 DOC-2/hDab2, 7 Ras GTPase activating protein, 8 telomerase activity, 9 apoptotic index, 10,11 and matrix metalloproteinases, 12 but no molecular parameter can currently replace serial serum human chorionic gonadotrophin (hCG) titers as the mainstay for predicting gestational trophoblastic neoplasia.…”

mentioning

confidence: 99%

Promoter Hypermethylation of Multiple Genes in Hydatidiform Mole and Choriocarcinoma

Xue

Chan

Feng

et al. 2004

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

The methylation status of genes in hydatidiform mole and choriocarcinoma and its significance is relatively unexplored. We investigated the methylation status of the promoter regions of six genes, p16, HIC-1, TIMP3, GSTP1, death-associated protein kinase (DAPK), and E-cadherin in 54 hydatidiform moles, five choriocarcinomas, and 10 first trimester placenta by methylation-specific polymerase chain reaction (PCR). Immunohistochemical expression of p16, TIMP3, and E-cadherin, and quantitative real-time RT-PCR of p16 was also performed. Among the six genes examined, the promoter region of four genes (E-cadherin, HIC-1, p16, TIMP3) in choriocarcinoma and three genes (E-cadherin, HIC-1, p16) in hydatidiform mole exhibited aberrant methylation whereas none was hypermethylated in normal placenta. There was a significant correlation between methylation and reduced expression of p16, E-cadherin, and TIMP3 (P < 0.001). Fifteen of the 54 patients with hydatidiform mole developed gestational trophoblastic neoplasia requiring chemotherapy. Promoter hypermethylation of p16 alone, or combined with E-cadherin, was significantly correlated to such development (P ‫؍‬ 0.001, 0.0005, respectively). Hypermethylation of multiple genes, especially p16, might be related to the subsequent development of gestational trophoblastic neoplasia. (J Mol Diagn 2004, 6:326 -334)

show abstract

mentioning

confidence: 99%

Promoter Hypermethylation of Multiple Genes in Hydatidiform Mole and Choriocarcinoma

Xue

Chan

Feng

et al. 2004

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

show abstract

“…Stronger MMP-2 expression has already been reported in CCAs than in placentas and HMs. 39 Our group has also documented down-regulation and promoter methylation of tissue inhibitor of metalloproteinase-3 in CCAs when compared with placentas. 40 The inductive effect of PAK1 on VEGF and MT1-MMP further explains the mechanisms governing cell invasion enhancing effect of PAK1.…”

Section: Discussionmentioning

confidence: 89%

p21-Activated Kinase-1 Promotes Aggressive Phenotype, Cell Proliferation, and Invasion in Gestational Trophoblastic Disease

Siu

Yeung

Zhang

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Gestational trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant tumor; placental site trophoblastic tumor; and epithelioid trophoblastic tumor. p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser 20 in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P ‫؍‬ 0.046) and HMs that developed persistent disease (P ‫؍‬ 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P ‫؍‬ 0.042) and choriocarcinomas (P ‫؍‬ 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P ‫؍‬ 0.016), and elevated PAK1 immunoreactivity was observed in placental site trophoblastic tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P ‫؍‬ 0.016) and MCM7 (P ‫؍‬ 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of

show abstract

“…While preeclampsia has been linked to a decrease of MMP-1 expression in placenta, umbilical serum and decidua, choriocarcinoma has been linked to an increase expression of MMP-1 in extravillous trophoblast (Cohen et al, 2012;Deng et al, 2015;Vegh et al, 1999), suggesting that US28 MMP-1 phenotype may be more related to cell survival. In transfected HUVECs, detectable levels of MMP-1 and MMP-10 were recorded, consistent with previous data showing upregulation of these mRNA upon exposure to inflammatory stimuli (Montero et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…decidua have been associated with both normal and abnormal pregnancies (Deng et al, 2015;Lockwood et al, 2014;Vegh et al, 1999;Xu et al, 2000). Here, concentration of nine MMP in the cell culture supernatant were analysed in two in vitro settings by Luminex assays.…”

Section: (A) (B)mentioning

confidence: 99%

Cell-type specific activities of cytomegalovirus GPCR homologues

Oliveira¹

View full text Add to dashboard Cite

The human cytomegalovirus (HCMV) is the main agent of congenital infection worldwide. Although primary infections or reactivations do not represent a threat to most individuals, they impose a lifethreating event to a developing foetus or immunocompromised individuals. Although we have learnt much about sites of viral replication and cells involved in the end-stage disease, the specific pathway and essential cell types that the virus must go through to later establish a successful infection and latency is still not clear. HCMV encodes four GPCR homologues (vGPCR): US27, US28, UL33 and UL78. vGPCR have been implicated in viral pathogenesis due to their ability to activate signalling pathways and, thus, alter physiological processes to favour infection. US28 and UL33 have been shown to activate several kinases and transcriptional factors. A key component of both US28 and UL33 sequence is the DRY (Asp/Arg/Tyr) motif, a region directly involved with G protein binding.Because Gα protein content is cell type-dependent, signalling activation by vGPCR can differ from cell to cell. Furthermore, these receptors share the particular characteristic of being constitutively Functional studies demonstrated migration induction of HTR-8 following transfection by either US28 or UL33. In order to investigate potential mechanisms, signalling pathways were probed via detection of activated kinases and the secretion of matrix metalloproteinases (MMP) and chemokines (CK) via luminex assays. Although differences in the level of kinases could not be measured by western blot, induction of MMP and CK were detected by Luminex assays, with contrasting results for US28 and UL33 in transfected cells (HTR-8 and HUVEC). An HCMV recombinant disrupted for US28 signalling (DQY) was generated and compared with wild type HCMV and a US28 null mutant for induction of MMP and CK in virus-infected cells. US28-dependent effects were identified for infected human foreskin fibroblasts, but results for HUVEC were equivocal.iii To determine potential bottlenecks to viral dissemination that may require M33 function(s), mice were infected with M33 knockout (M33) viruses by different routes: intranasal, -mimicking the most natural route, footpad -a more compartmentalized route, and intraperitoneal, the most direct route to major organs. To help track viral dissemination, a luciferase tagged M33 was generated and infection was compared to control virus (M78luc). M33 intranasal infection did not result in attenuation for colonisation of the nose, draining (superficial cervical) lymph nodes (dLN) or the lungs. Via footpad route, M33 colonised the footpad and dLN to levels equivalent to control virus, but was significantly attenuated in spread to the spleen and, subsequently, the salivary glands.Following intraperitoneal infection, the virus is readily delivered to major organs due to direct access to the bloodstream, there was no difference in the colonisation of primary organs (spleen, liver) between M33 and control MCMV, but M33 was still unable ...

show abstract

Matrix Metalloproteinases and Their Inhibitors in Gestational Trophoblastic Diseases and Normal Placenta

Cited by 49 publications

References 22 publications

Promoter Hypermethylation of Multiple Genes in Hydatidiform Mole and Choriocarcinoma

Promoter Hypermethylation of Multiple Genes in Hydatidiform Mole and Choriocarcinoma

p21-Activated Kinase-1 Promotes Aggressive Phenotype, Cell Proliferation, and Invasion in Gestational Trophoblastic Disease

Cell-type specific activities of cytomegalovirus GPCR homologues

Contact Info

Product

Resources

About