Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Molecular Cancer, Год журнала: 2021, Номер 20(1)

Опубликована: Окт. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Язык: Английский

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Tumor microenvironment complexity and therapeutic implications at a glance

Cell Communication and Signaling, Год журнала: 2020, Номер 18(1)

Опубликована: Апрель 7, 2020

Abstract The dynamic interactions of cancer cells with their microenvironment consisting stromal (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity cell, clonal evolution increase multidrug resistance ending in cell progression metastasis. reciprocal cell-cell/ECM interaction tumor hijacking non-malignant force lose function acquire new phenotypes that promote development invasion cells. Understanding underlying cellular molecular mechanisms governing these can be used as a novel strategy indirectly disrupt interplay contribute efficient safe therapeutic strategies fight cancer. Furthermore, tumor-derived circulating materials also diagnostic tools precisely predict monitor outcome therapy. This review evaluates such potentials various advanced models, focus on 3D systems well lab-on-chip devices.

Язык: Английский

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The Dark Side of Fibroblasts: Cancer-Associated Fibroblasts as Mediators of Immunosuppression in the Tumor Microenvironment

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Авг. 2, 2019

Cancer-associated fibroblasts (CAFs) are prominent components of the microenvironment in most types solid tumors, and were shown to facilitate cancer progression by supporting tumor cell growth, extracellular matrix remodeling, promoting angiogenesis, mediating tumor-promoting inflammation. In addition an inflammatory microenvironment, tumors characterized immune evasion immunosuppressive milieu. recent years, CAFs emerging as central players regulation that shapes microenvironment. contribute escape via multiple mechanisms, including secretion cytokines chemokines reciprocal interactions mediate recruitment functional differentiation innate adaptive cells. Moreover, directly abrogate function cytotoxic lymphocytes, thus inhibiting killing this review, we focus on advancements our understanding how drive fate tumor-infiltrating cells towards provide outlook future therapeutic implications may lead integration preclinical findings into design novel combination strategies, aimed at impairing tumor-supportive CAFs.

Язык: Английский

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Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 146 - 146

Опубликована: Дек. 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.

Язык: Английский

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Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Март 24, 2022

Abstract Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor stromal cells to promote proliferation, migration, invasion, angiogenesis immune evasion. Both ECM itself stiffening-induced mechanical stimuli may activate cell membrane receptors mechanosensors such as integrin, Piezo1 TRPV4, thereby modulating the malignant phenotype of cells. A better understanding how stiffness regulates progression will contribute development new therapeutics. rapidly expanding evidence in this research area suggests that regulators effectors represent potential therapeutic targets cancer. This review summarizes recent work on regulation cancer, effects progression, immunity drug resistance. We also discuss be druggable intervene Based these advances, future efforts can made develop more effective safe drugs interrupt stiffness-induced oncogenic signaling,

Язык: Английский

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Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Апрель 15, 2020

The tumor microenvironment (TME) is composed of various cell types embedded in an altered extracellular matrix (ECM). ECM not only serves as a support for but also regulates cell-cell or cell-matrix cross-talks. Alterations may be induced by hypoxia and acidosis, oxygen free radicals generated infiltrating inflammatory cells tumor- stromal cell-secreted proteases. A poorer diagnosis patients often associated with alterations. Tumor proteome, named cancer matrisome, strongly altered, different protein signatures defined to serve prognostic biomarkers. Collagen network reorganization facilitates invasion. Proteoglycan expression location are modified the TME affect invasion metastatic dissemination. macromolecule degradation proteases induce release angiogenic growth factors proteoglycan-derived fragments, matrikines matricryptins. This review will focus on current knowledge new insights alterations, degradation, reticulation through cross-linking enzymes role fragments control progression their potential use biomarkers prognosis.

Язык: Английский

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Mechanoresponsive metabolism in cancer cell migration and metastasis

Cell Metabolism, Год журнала: 2021, Номер 33(7), С. 1307 - 1321

Опубликована: Апрель 28, 2021

Язык: Английский

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Tumor microenvironment components: Allies of cancer progression

Pathology - Research and Practice, Год журнала: 2019, Номер 216(1), С. 152729 - 152729

Опубликована: Ноя. 11, 2019

Язык: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Язык: Английский

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The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cancers, Год журнала: 2021, Номер 13(18), С. 4720 - 4720

Опубликована: Сен. 21, 2021

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, therapy resistance. As metastasis is main reason for cancer-related deaths, it crucial understand the of CAFs this process. Colorectal (CRC) heterogeneous disease lethality especially common subtype CRC high stromal infiltration. A component stroma cancer-associated (CAFs). To provide new perspectives research on CAF-targeted therapeutics, CRC, we discuss mechanisms, crosstalk, functions involved CAF-mediated protection. This summary can serve as framework future studies elucidating these roles CAFs.

Язык: Английский

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