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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Exosomes: key players in cancer and potential therapeutic strategy

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Авг. 5, 2020

Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular etc., which play a crucial role regulating tumor growth, metastasis, angiogenesis the process cancer development, can be used as prognostic marker and/or grading basis for patients. Hereby, we mainly summarized followed: exosome contents cancer, focusing on proteins RNA; interaction between exosomes microenvironment; mechanisms that epithelial-mesenchymal transition, invasion migration affected exosomes; suppression strategies based exosomes. Finally, application potential clinical diagnosis therapy is prospected, providing theoretical supports using to serve precise treatment clinic.

Язык: Английский

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Exosome Processing and Characterization Approaches for Research and Technology Development

Advanced Science, Год журнала: 2022, Номер 9(15)

Опубликована: Март 25, 2022

Exosomes are extracellular vesicles that share components of their parent cells and attractive in biotechnology biomedical research as potential disease biomarkers well therapeutic agents. Crucial to realizing this is the ability manufacture high-quality exosomes; however, unlike biologics such proteins, exosomes lack standardized Good Manufacturing Practices for processing characterization. Furthermore, there a well-characterized reference exosome materials aid selection methods isolation, purification, analysis. This review informs technology development by comparing characterization recommending workflows. also provides detailed introduction exosomes, including physical chemical properties, roles normal biological processes progression, summarizes some on-going clinical trials.

Язык: Английский

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Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy

Advanced Materials, Год журнала: 2020, Номер 32(51)

Опубликована: Окт. 5, 2020

Abstract Exosomes are a class of extracellular vesicles around 100 nm in diameter that secreted by most cells and contain various bioactive molecules reflecting their cellular origin mediate intercellular communication. Studies these exosomal features tumor pathogenesis have led to the development therapeutic diagnostic approaches using exosomes for cancer therapy. many advantages conveying agents such as small interfering RNAs, microRNAs, membrane‐associated proteins, chemotherapeutic compounds; thus, they considered prime candidate delivery tool treatment. Since also provide an optimal microenvironment effective function immunomodulatory factors, harboring been bioengineered immunotherapies can effectively activate each stage immunity cycle successfully elicit cancer‐specific immunity. This review discusses treating challenges must be overcome successful clinical development.

Язык: Английский

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Exosomes: roles and therapeutic potential in osteoarthritis

Bone Research, Год журнала: 2020, Номер 8(1)

Опубликована: Июнь 19, 2020

Exosomes participate in many physiological and pathological processes by regulating cell-cell communication, which are involved numerous diseases, including osteoarthritis (OA). detectable the human articular cavity were observed to change with OA progression. Several joint cells, chondrocytes, synovial fibroblasts, osteoblasts, tenocytes, can produce secrete exosomes that influence biological effects of targeted cells. In addition, from stem cells protect damage promoting cartilage repair, inhibiting synovitis, mediating subchondral bone remodeling. This review summarizes roles therapeutic potential discusses perspectives challenges related exosome-based treatment for patients future.

Язык: Английский

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Using single-vesicle technologies to unravel the heterogeneity of extracellular vesicles

Nature Protocols, Год журнала: 2021, Номер 16(7), С. 3163 - 3185

Опубликована: Июнь 16, 2021

Язык: Английский

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Designer Exosomes: A New Platform for Biotechnology Therapeutics

BioDrugs, Год журнала: 2020, Номер 34(5), С. 567 - 586

Опубликована: Авг. 4, 2020

Язык: Английский

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Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis

Hepatology, Год журнала: 2019, Номер 70(4), С. 1317 - 1335

Опубликована: Апрель 15, 2019

Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote progression chronic cholestatic liver diseases. We previously reported that cholangiocyte-derived exosomal long noncoding RNA-H19 (lncRNA-H19) plays a critical role in promoting injury. However, it remains unclear whether lncRNA-H19 regulates HSC activation, which is major focus this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2-/- ) mouse models were used. Wild-type H19maternalΔExon1/+ (H19KO) mice subjected BDL. Mdr2-/- (DKO) generated. Exosomes isolated from cultured human cholangiocytes or serum used for vivo transplantation vitro studies. Fluorescence-labeled exosomes flow cytometry monitor exosome uptake by cells. Collagen gel contraction bromodeoxyuridine assays determine effect exosomal-H19 on activation proliferation. Mouse sclerosing cholangitis (PSC)/primary biliary (PBC) samples analyzed real-time PCR, western blot analysis, histology, immunohistochemistry. The results demonstrated H19 level was closely correlated with severity fibrosis both patients PSC PBC. deficiency significantly protected BDL mice. Transplanted H19-enriched rapidly preferentially taken up HSCs HSC-derived fibroblasts, promoted BDL-H19KO DKO enhanced transdifferentiation proliferation matrix formation fibroblasts. Conclusion: Cholangiocyte-derived differentiation potential diagnostic biomarker therapeutic target cholangiopathies.

Язык: Английский

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Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(18), С. 4588 - 4588

Опубликована: Сен. 17, 2019

Extracellular heat shock proteins (ex-HSPs) have been found in exosomes, oncosomes, membrane surfaces, as well free HSP cancer and various pathological conditions, also known alarmins. Such ex-HSPs include HSP90 (α, β, Gp96, Trap1), HSP70, large small HSPs. Production of HSPs is coordinately induced by factor 1 (HSF1) hypoxia-inducible (HIF-1), while matrix metalloproteinase 3 (MMP-3) heterochromatin protein are novel inducers Oncosomes released tumor cells a major aspect the resistance-associated secretory phenotype (RASP) which immune evasion can be established. The concepts RASP are: (i) releases ex-HSP HSP-rich oncosomes essential RASP, molecular co-transfer with oncogenic factors to recipient promote progression resistance against stresses such hypoxia, radiation, drugs, systems; (ii) eject anticancer targeted therapeutics, checkpoint inhibitors oncosomes; (iii) cytotoxic lipids from RASP. membrane-surface (mHSP) play immunostimulatory roles recognized CD91+ scavenger receptor expressed endothelial cells-1 (SREC-1)+ Toll-like receptors (TLRs)+ antigen-presenting cells, leading antigen cross-presentation T cell cross-priming, CD94+ natural killer cytolysis. On other hand, ex-HSP/CD91 signaling promotes progression. body fluids potential biomarkers detectable liquid biopsies cancers tissue-damaged diseases. HSP-based vaccines, inhibitors, RNAi therapeutics reviewed.

Язык: Английский

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Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions

Cancers, Год журнала: 2020, Номер 12(5), С. 1232 - 1232

Опубликована: Май 14, 2020

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular well signal molecules mediators. Tumor cells recruit reprogram other to produce factors that maintain growth. Communication between cancerous surrounding two-way process engages diverse range mechanisms that, in consequence, can lead rapid proliferation, metastasis, drug resistance, or serve tumors-suppressor, e.g., through tumor–immune cell interaction. Cross-talk within the cancer be direct by cell-to-cell contact via adhesion molecules, electrical coupling, passage gap junctions, indirect classical paracrine signaling cytokines, growth factors, extracellular vesicles. Therapeutic approaches for modulation cell-cell communication may promising strategy combat tumors. In particular, integrative targeting combination with conventional chemotherapy seem reasonable. Currently, special attention paid suppressing formation open-ended channels blocking exosome production ablating their cargos. However, many aspects have yet clarified, and, more work needed regard bidirectional transfer. Finally, it seems some interactions TEM not only cancer-specific, but also patient-specific, recognition would help predict patient response therapy.

Язык: Английский

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