Abstract:
:As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those associated with cell-cell and cell-matrix adhesion, with the degradation of extracellular matrix, and with the initiation and maintenance of early growth at the new site are generally accepted to be critical. This article discusses current knowledge of molecular events involved in these various processes. The potential role of adhesion molecules (eg. integrins and cadherins) has undergone a major transition over the last ten years, as it has become apparent that such molecules play a major role in signaling from outside to inside a cell, thereby controlling how a cell is able (or not) to sense and interact with its local environment. Similarly the roles of proteolytic enzymes and their inhibitors (eg. matrix metalloproteinases and TIMPs) have also expanded as it has become apparent that they not only have the abilities to break down the components of the extracellular matrix but also are involved in the release of factors which can affect the growth of the tumor cells positively or negatively. Recent work has highlighted the importance of the later, post-extravasational stages of metastasis, where adhesion and proteolysis are now known to play a role along with other processes such as apoptosis, dormancy, growth factor-receptor interactions and signal transduction. Recent work has also demonstrated that not only the immediate cellular microenvironment, in terms of specific cell-cell and cell-matrix interactions, but also the extended cellular microenvironment, in terms of vascular insufficiency and hypoxia in the primary tumor, can modify cellular gene expression and enhance metastasis. Mechanisms of metastasis appear to involve a complex array of genetic and epigenetic changes many of which appear to be specific both for different types of tumors and for different sites of metastasis. Our improved understanding of the expanded roles of the individual molecules involved has resulted in a mechanistic blurring of the previously described discrete stages of the metastatic process.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Cairns RA,Khokha R,Hill RPdoi
10.2174/1566524033479447keywords:
subject
Has Abstractpub_date
2003-11-01 00:00:00pages
659-71issue
7eissn
1566-5240issn
1875-5666journal_volume
3pub_type
杂志文章,评审abstract::Diabetic complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis. Chronic hyperglycemia is initially involved in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic derangements. High glucose increa...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406776894536
更新日期:2006-05-01 00:00:00
abstract::Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage an...
journal_title:Current molecular medicine
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更新日期:2012-12-01 00:00:00
abstract::Pancreatic Adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide. A variety of mechanisms are involved in PDAC biological behaviors, of which, the mechanisms of immune escape may be a pivotal hallmark. HLA-G is a tolerant molecule implicated in tumor escape and serves as a prognostic biomarker in ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150401102218
更新日期:2015-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666180705114131
更新日期:2018-01-01 00:00:00
abstract::Enteroviruses are common human pathogens involved in a wide spectrum of clinical outcomes ranging from mild or non-symptomatic illness to severe diseases with neurological and/or cardiac manifestation. Despite being responsible for significant morbidity and mortality especially in immunocompromised patients and infant...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011009060550
更新日期:2010-08-01 00:00:00
abstract::The purpose of this review is to provide a concise overview of developments over the last 15 years in the field of laboratory tests in human medicine that are based on the detection of alterations in the glycan part of glycoconjugates. We show how glycosylation-based diagnostic testing is widespread in the current cli...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407780831629
更新日期:2007-06-01 00:00:00
abstract::Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizer...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479672
更新日期:2003-08-01 00:00:00
abstract::HMGB1/Amphoterin is a ubiquitous, highly conserved DNA-binding protein that can be also released to the extracellular space by various cell types. Extracellular HMGB1 regulates migratory responses of several cell types through binding to RAGE that communicates with the cytoskeleton to regulate cell motility. HMGB1-ind...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407783220750
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. METHOD:In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursode...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200123161340
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. METHODS:Whole-mount in situ hybridization and embryo immunostaining were performed. RESULTS:Zebrafish Fhl1A is the homologue of human F...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180308113909
更新日期:2017-01-01 00:00:00
abstract::Spider venom is a large pharmacological repertoire containing many biologically active peptides, which may have a potent therapeutic implication. Here we investigated a peptide toxin, named lycosin-I, isolated from the venom of the spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting inhibito...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412803833643
更新日期:2012-12-01 00:00:00
abstract::Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362041
更新日期:2002-11-01 00:00:00
abstract::The acquisition of cellular immortality is a critical step in human tumorigenesis. While the vast majority of human tumors activate the catalytic component of telomerase (hTERT) to stabilize their telomeres and attain immortality, a significant portion (7-10%) utilize a poorly defined alternative form of telomere main...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053586653
更新日期:2005-03-01 00:00:00
abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795677963
更新日期:2011-06-01 00:00:00
abstract::Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412798376125
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Osteoporosis is a systemic skeletal disease characterized by low bone mineral density. Vitamin D metabolism may play a pivotal role in its pathophysiology. OBJECTIVES:To determine the association between Vitamin D receptor gene polymorphisms and bone density, as well as its relation to biochemical markers o...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190409122155
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Lauric acid (LA) has antimicrobial effects and the potential to replace antibiotics in feeds to prevent postweaning diarrhea and increase overall swine productivity. The effects of lauric acid on the intestinal epithelial cells remain unclear. METHODS AND RESULTS:This study investigates the effects of LA on...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200128155115
更新日期:2020-01-01 00:00:00
abstract::Preeclampsia is a disease of high incidence in pregnant women which complicates pregnancy and may lead to the death of mother and baby. Preeclampsia is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction. Although the causes of disease have not be...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/15665240113139990058
更新日期:2013-09-01 00:00:00
abstract::Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cell...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787314471
更新日期:2009-02-01 00:00:00
abstract::HIV infection causes an acquired immunodeficiency, principally because of depletion of CD4 lymphocytes. The mechanism by which the virus depletes these cells, however, is not clearly understood. Since the virus predominantly infects CD4 lymphocytes in vivo, some have assumed that HIV replication directly kills the inf...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013363320
更新日期:2001-11-01 00:00:00
abstract::A major benefit of the genomics revolution in biomedical research has been the establishment of transcriptome analysis as an enabling technology in the drug development process. Nowhere in the realm of drug development has the expectation of the impact of transcriptome analysis been greater than in the area of pre-cli...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053152825
更新日期:2005-02-01 00:00:00
abstract::Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652411796268731
更新日期:2011-08-01 00:00:00
abstract::By eliminating the unneeded or mutant cells, programmed cell death actively participates in a wide range of biological processes from embryonic development to homeostasis maintenance in adult. Continuing efforts have identified multiple cell death pathways, with apoptosis, necrosis and autophage the mostly studied. Re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666151026100339
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190918160032
更新日期:2019-01-01 00:00:00
abstract::Multiple myeloma (MM) is characterized by the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and g...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666181008112738
更新日期:2018-01-01 00:00:00
abstract::Strong epidemiological evidence indicates that migraine, especially migraine with aura, is associated with increased risk of ischemic stroke. However, the precise mechanisms of such a relation are currently not fully elucidated and are still a matter of speculation. Migraine may directly cause an ischemic event (i.e, ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787581583
更新日期:2009-03-01 00:00:00
abstract::Charcot-Marie-Tooth disease (CMT) and related neuropathies are a genetically highly heterogeneous group of neurodegenerative disorders. CMT affects both the sensory and motor nerves, distal Hereditary Motor Neuropathies (dHMN) are phenotypically similar disorders involving only motor nerves, while Hereditary Sensory a...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141010154205
更新日期:2014-01-01 00:00:00
abstract::Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605761
更新日期:2002-03-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150330142807
更新日期:2015-01-01 00:00:00
abstract::Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established. Recently, the overexpression of this re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781695765
更新日期:2007-09-01 00:00:00