The Functional Role of Extracellular Matrix Proteins in Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(1), P. 238 - 238

Published: Jan. 4, 2022

The extracellular matrix (ECM) is highly dynamic as it constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM a major structural component of the tumor microenvironment, cancer development progression require its extensive reorganization. Cancerized biochemically different in composition stiffer compared normal ECM. abnormal affects by directly promoting cell proliferation, survival, migration differentiation. restructured degradation fragments (matrikines) also modulate signaling cascades mediated interaction with cell-surface receptors, deregulate stromal behavior lead emergence an oncogenic microenvironment. Here, we summarize current state understanding how structure changes during progression. We describe functional role key proteins, especially tenascin C fibronectin, molecules involved formation well pathways that they activate cells.

Language: Английский

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Novel approaches to target the microenvironment of bone metastasis

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(8), P. 488 - 505

Published: April 19, 2021

Language: Английский

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Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?

Cancers, Journal Year: 2021, Volume and Issue: 13(14), P. 3466 - 3466

Published: July 11, 2021

Solid cancer progression is dictated by neoplastic cell features and pro-tumoral crosstalks with their microenvironment. Stroma modifications, such as fibroblast activation into cancer-associated fibroblasts (CAFs) extracellular matrix (ECM) remodeling, are now recognized critical events for potential therapeutic or diagnostic targets. The recent appreciation of the key, complex multiple roles ECM in CAF diversity, has revolutionized field raised innovative but challenging questions. Here, we rapidly present heterogeneity link specific remodeling observed cancer, before developing each impacts modifications on tumor (survival, angiogenesis, pre-metastatic niche, chemoresistance, etc.), patient prognosis. Finally, based preclinical studies results obtained from clinical trials, highlight key mechanisms proteins that are, may be, used targets, report discuss benefits, disappointments, even failures, recently reported stroma-targeting strategies.

Language: Английский

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Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(3), P. 829 - 868

Published: Jan. 1, 2022

Photoacoustic (PA) imaging has emerged as a powerful technique for the high resolution visualization of biological processes within deep tissue. Through development and application exogenous targeted contrast agents activatable probes that can respond to given cancer biomarker, researchers image molecular events

Language: Английский

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The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(9), P. 101170 - 101170

Published: Aug. 30, 2023

The tumor microenvironment (TME) is influenced by a "disorganized" extracellular matrix (ECM) that sensitizes cancer cells toward mechanical stress, signaling, and structural alterations. In hepatocellular carcinoma (HCC), lack of knowledge about key ECM proteins driving the TME refractory to targeted therapies poses barrier identification new therapeutic targets. Herein, we discuss contributions various components impact hepatocytes their surrounding support network during tumorigenesis. addition, underpinnings which transduce signals liver are detailed. Finally, in view bidirectional feedback between ECM, transformed hepatocytes, immune cells, highlight potential role disorganization process shaping responses checkpoint inhibitors therapies. Our comprehensive characterization these may provide roadmap for innovative approaches restrain HCC.

Language: Английский

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Extracellular matrix remodeling in the tumor immunity

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 25, 2024

The extracellular matrix (ECM) is a significant constituent of tumors, fulfilling various essential functions such as providing mechanical support, influencing the microenvironment, and serving reservoir for signaling molecules. abundance degree cross-linking ECM components are critical determinants tissue stiffness. In process tumorigenesis, interaction between immune cells within tumor microenvironment (TME) frequently leads to stiffness, thereby disrupting normal mechanotransduction promoting malignant progression. Therefore, acquiring thorough comprehension dysregulation TME would significantly aid in identification potential therapeutic targets cancer treatment. this regard, we have compiled comprehensive summary encompassing following aspects: (1) principal their roles conditions; (2) intricate TME; (3) pivotal regulators governing onco-immune response ECM.

Language: Английский

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Role of the Extracellular Matrix in Cancer: Insights into Tumor Progression and Therapy

Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract The extracellular matrix (ECM) serves not only as a structural scaffold but also an active regulator of cancer progression, profoundly influencing tumor behaviour and the microenvironment (TME). This review focuses into pivotal role ECM alterations in facilitating metastasis explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis disrupt associated signalling pathways critical for architecture cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods suppress synthesis enzymatic degrade it, thereby mitigating tumor‐promoting effects. discussion extends innovative modulating stiffness, focusing on roles cancer‐associated fibroblasts lysyl oxidases, which key contributors remodelling mechanical signalling. By strategically modifying components, aim enhance efficacy existing treatments, tackle resistance mechanisms, achieve more durable outcomes. Insights from recent studies clinical trials highlight promise overcoming treatment improving patient Advancing our understanding biology leads development effective therapies.

Language: Английский

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Shaping Up the Tumor Microenvironment With Cellular Fibronectin

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: April 30, 2020

Normal tissue homeostasis and architecture restrain tumor growth. Thus for a to develop spread, malignant cells must overcome growth-repressive inputs from surrounding escape immune surveillance mechanisms that curb cancer progression. This is achieved by promoting the conversion of physiological microenvironment pro-tumoral state it requires constant dialog between ostensibly normal adjacent tissue. Pro-tumoral reprogramming stroma accompanied an upregulation certain extracellular matrix (ECM) proteins their cognate receptors. Fibronectin (FN) one such component matrisome. large multidomain glycoprotein dimer expressed over wide range human cancers assembled cell-driven forces into fibrillar array provides obligate scaffold deposition other binding sites functionalization soluble factors in microenvironment. Encoded single gene, FN regulates proliferation, motile behavior fate multiple cell types, largely through involve integrin-mediated signaling. These processes are coordinated distinct isoforms FN, collectively known as cellular (as opposed circulating plasma FN) arise alternative splicing FN1 gene. Cellular differ solubility, receptor ability spatiotemporal expression, exert functions have yet be fully defined. induction at constitutes important step acquisition biological capabilities required several hallmarks sustaining proliferative signaling, angiogenesis, facilitating invasion metastasis, modulating growth suppressor activity regulating anti-tumoral immunity. In this review, we will first provide overview ECM tumor-stroma crosstalk then focus on role progression with respect these hallmarks. Last, discuss impact dysregulated clinical efficacy classical (radio-/chemo-) therapies emerging treatments target checkpoints explore how our growing knowledge central can leveraged therapeutic benefit.

Language: Английский

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Explaining decisions of graph convolutional neural networks: patient-specific molecular subnetworks responsible for metastasis prediction in breast cancer

Genome Medicine, Journal Year: 2021, Volume and Issue: 13(1)

Published: March 11, 2021

Abstract Background Contemporary deep learning approaches show cutting-edge performance in a variety of complex prediction tasks. Nonetheless, the application healthcare remains limited since methods are often considered as non-interpretable black-box models. However, machine community made recent elaborations on interpretability explaining data point-specific decisions techniques. We believe that such explanations can assist need personalized precision medicine via patient-specific predictions. Methods Layer-wise Relevance Propagation (LRP) is technique to explain methods. It widely used interpret Convolutional Neural Networks (CNNs) applied image data. Recently, CNNs started extend towards non-Euclidean domains like graphs. Molecular networks commonly represented graphs detailing interactions between molecules. Gene expression be assigned vertices these In other words, gene structured by utilizing molecular network information prior knowledge. Graph-CNNs data, for example, predict metastatic events breast cancer. Therefore, there showing which part relevant predicting an event, e.g., distant metastasis cancer, each individual patient. Results extended procedure LRP make it available Graph-CNN and tested its applicability large cancer dataset. present Graph (GLRP) new method Graph-CNNs. demonstrate sanity check developed GLRP hand-written digits dataset then apply provides subnetworks largely agree with clinical knowledge identify common well novel, potentially druggable, drivers tumor progression. Conclusions The could highly useful interpreting classification results context different omics patient level, example or board.

Language: Английский

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The Dynamic Relationship of Breast Cancer Cells and Fibroblasts in Fibronectin Accumulation at Primary and Metastatic Tumor Sites

Cancers, Journal Year: 2020, Volume and Issue: 12(5), P. 1270 - 1270

Published: May 17, 2020

In breast cancer (BC), tissue stiffening via fibronectin (FN) and collagen accumulation is associated with advanced disease progression at both the primary tumor metastatic sites. Here, we evaluate FN production in 15 BC cell lines, representing a variety of subtypes, phenotypes, potentials, chemotherapeutic sensitivities. We demonstrate that intracellular soluble initially lost during tumorigenic transformation but rescued all lines epithelial-mesenchymal plasticity (EMP). Importantly, establish no line was able to independently organize robust matrix. Non-transformed mammary epithelial cells were also unable deposit matrices unless transglutaminase 2, crosslinking enzyme, overexpressed. Instead, manipulated matrix fibroblasts phenotypic-dependent manner. addition, varied levels seen depending if conditioned model paracrine signaling or endocrine niche. former, by cultures high EMP resulted largest accumulation. contrast, mesenchymal produced extracellular vesicles (EV) highest formation fibroblasts. Overall, dynamic relationship between stromal within microenvironment, which fibrillarization are modulated particular stages progression.

Language: Английский

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