Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Language: Английский

---

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 23(1), P. 146 - 146

Published: Dec. 23, 2021

Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, turnover by degrading extracellular (ECM) components releasing matrikines, surface-bound cytokines, growth factors, or their receptors. Among MMPs, MMP-14 is driving force behind destruction during cancer invasion metastasis. also influences both intercellular as well cell-matrix communication regulating many plasma membrane-anchored proteins. cells other stroma, embedded in a common matrix, interact means various adhesive structures, particularly invadopodia are capable to remodel through spatially temporally finely tuned proteolysis. As deeper understanding underlying functional mechanisms beneficial for development new prognostic predictive markers targeted therapies, this review examined current knowledge interplay MMPs context protein, subcellular, cellular level focus MMP14.

Language: Английский

---

Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(3), P. 714 - 770

Published: June 23, 2022

The first matrix metalloproteinase (MMP) was discovered in 1962 from the tail of a tadpole by its ability to degrade collagen. As their name suggests, metalloproteinases are proteases capable remodeling extracellular matrix. More recently, MMPs have been demonstrated play numerous additional biologic roles cell signaling, immune regulation, and transcriptional control, all which unrelated degradation In this review, we will present milestones major discoveries MMP research, including various clinical trials for use inhibitors. We discuss reasons behind failures most inhibitors treatment cancer inflammatory diseases. There still misconceptions about pathophysiological best strategies inhibit detrimental functions. This review aims preclinical models human pathologies. new biochemical tools track proteolytic activity vivo ex vivo, addition future pharmacological alternatives functions

Significance Statement

Matrix (MMPs) implicated inflammatory, autoimmune, cancers, pathogen-mediated Initially overlooked, contributions can be both beneficial disease progression resolution. Thousands substrates suggested, few hundred validated. After more than 60 years there remain intriguing enigmas solve regarding biological

Language: Английский

---

Pathological angiogenesis: mechanisms and therapeutic strategies

Angiogenesis, Journal Year: 2023, Volume and Issue: 26(3), P. 313 - 347

Published: April 15, 2023

In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, coalescent well vessel co-option, vasculogenic mimicry lymphangiogenesis, underlie vasculature. many pathological conditions, cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but often done so without normal feedback that regulate ordinary spatial temporal patterns formation. Thus, angiogenesis presents challenges yet opportunities design vascular-directed therapies. Here, we provide overview recent insights into development highlight novel therapeutic strategies promote or inhibit to stabilize, reverse, even halt disease progression. our review, will also explore several additional aspects (the switch, hypoxia, angiocrine signals, endothelial plasticity, normalization, cell anergy) operate in parallel canonical speculate how these may be targeted with anti-angiogenic

Language: Английский

---

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1938 - 1938

Published: Aug. 10, 2022

Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs chronic can remain hidden for a long time. Moreover, leading cause of global morbidity mortality, thus creating public health concern. This review summarizes available information on pathophysiological implications CVDs, focusing coronary artery disease along atherosclerosis as arterial hypertension. We discuss endothelium dysfunction, inflammatory factors, oxidation atherosclerosis. Mechanisms such dysfunction inflammation, which have been identified critical pathways development disease, become easier to diagnose in recent years. Relatively recently, evidence has found indicating that interactions molecular cellular elements matrix metalloproteinases, immune system, oxidative stress involved pathophysiology Many studies revealed several important genetic risk factors CVDs. However, further investigation crucial improve our knowledge progression and, more importantly, accelerate basic research understanding mechanism pathophysiology.

Language: Английский

---

Identifying multicellular spatiotemporal organization of cells with SpaceFlow

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 14, 2022

One major challenge in analyzing spatial transcriptomic datasets is to simultaneously incorporate the cell transcriptome similarity and their locations. Here, we introduce SpaceFlow, which generates spatially-consistent low-dimensional embeddings by incorporating both expression information using spatially regularized deep graph networks. Based on embedding, a pseudo-Spatiotemporal Map that integrates pseudotime concept with locations of cells unravel spatiotemporal patterns cells. By comparing multiple existing methods several at spot single-cell resolutions, SpaceFlow shown produce robust domain segmentation identify biologically meaningful patterns. Applications reveal evolving lineage heart developmental data tumor-immune interactions human breast cancer data. Our study provides flexible learning framework

Language: Английский

---

Insights Into the Role of Matrix Metalloproteinases in Cancer and its Various Therapeutic Aspects: A Review

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 29, 2022

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate the turnover of extracellular matrix (ECM) components. Gross and La Piere discovered MMPs in 1962 during an experiment on tissue samples from a tadpole’s tail. Several subtypes have been identified, depending their substrate specificity localization. involved as essential molecules multiple diverse physiological processes, such reproduction, embryonic development, bone remodeling, repair, regulation inflammatory processes. Its activity is controlled at various levels transcription level, pro-peptide activation level by family inhibitors metalloproteinase, endogenous MMPs. Cancer metastasis, which spread tumor to distant site, complex process responsible for majority cancer-related death It considered be indicator cancer metastasis. During cells invade blood vessel degrade ECM make path new loci places. The degradation vessels mediated through Hence, MMP critical determining metastatic potential cell. Evasion apoptosis one hallmarks found correlated with expression As result, given importance cancer, we describe role these multifunctional enzymes aspects formation rising possibilities novel therapeutic target this review. There also brief discussion types components drugs function against

Language: Английский

---

Dual mode fluorometric and colorimetric detection of matrix metalloproteinase MMP-9 as a cancer biomarker based on AuNPs@gelatin/AuNCs nanocomposite

Biosensors and Bioelectronics, Journal Year: 2022, Volume and Issue: 220, P. 114889 - 114889

Published: Nov. 5, 2022

Language: Английский

---

Carboranes as unique pharmacophores in antitumor medicinal chemistry

Molecular Therapy — Oncolytics, Journal Year: 2022, Volume and Issue: 24, P. 400 - 416

Published: Jan. 10, 2022

Carborane is a carbon-boron molecular cluster that can be viewed as 3D analog of benzene. It features special physical and chemical properties, thus has the potential to serve new type pharmacophore for drug design discovery. Based on relative positions two cage carbons, icosahedral closo-carboranes classified into three isomers, ortho-carborane (o-carborane, 1,2-C2B10H12), meta-carborane (m-carborane, 1,7-C2B10H12), para-carborane (p-carborane, 1,12-C2B10H12), all them deboronated generate their nido- forms. Cage compound carborane its derivatives have been demonstrated useful entities in antitumor medicinal chemistry. The applications carboranes field research mainly include boron neutron capture therapy (BNCT), BNCT/photodynamic dual sensitizers, anticancer ligands. This review summarizes progress achieved up October 2021, with particular emphasis signaling transduction pathways, structures, mechanistic considerations using carboranes.

Language: Английский

---

Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 27, 2023

Impaired wound healing is the most common and significant complication of Diabetes. While other complications Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain suffering in patients. Wound closure repair are orchestrated by sequence events aided release pro-inflammatory cytokines, which dysregulated cases Diabetes, making environment unfavorable for delaying processes. This concise review provides an overview dysregulation cytokines offers insights into therapeutic outcomes.

Language: Английский

---