Exosomes: Dynamic Mediators of Extracellular Communication in the Tumor Microenvironment

Wolf-Dennen, Kerri; Kleinerman, Eugenie S.

doi:10.1007/978-3-030-43085-6_13

Cited by 16 publications

(10 citation statements)

References 87 publications

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“…Meanwhile, abnormal tumor blood vessels reduce the delivery of drugs into tumor tissues, which ultimately leads to limited efficacy of anti-cell proliferation therapy. Therefore, the treatment for cancer should not only be directed against tumor cells, but also against the tumor microenvironment, in particularly tumor angiogenesis ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

Zheng

Wang

Hou

et al. 2021

Front. Cardiovasc. Med.

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Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.

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Section: Introductionmentioning

confidence: 99%

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

Zheng

Wang

Hou

et al. 2021

Front. Cardiovasc. Med.

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“…Exosomes are important components that constitute the tumor microenvironment and can participate in angiogenesis to accelerate tumor progression through intercellular information communication [ 24 , 25 ]. For example, mesenchymal stem cells undergo morphological and functional alterations under the stimulation of exosomes secreted by colorectal cancer cells, and this change will further affect tumor cell growth and metastasis [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of non-small cell lung cancer cells

Wen

Liu

Tang

et al. 2021

Aging

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Introduction: Non-small cell lung cancer (NSCLC) is the most common malignant tumor, and its recurrence and metastasis are the main causes of death. Recently, there is evidence that tumor derived exosomes play an important role in the occurrence and development of NSCLC. Objective’s methods: First, the expression of miR-185-5p and RAB35 in NSCLC tissues, paracancerous tissues, NSCLC cell lines and normal human bronchial epithelial cell line was detected. Then, a series of gain-and loss-of-function assays were performed to validate the effects of miR-185-5p or RAB35 effects on A549 and H2170 cells proliferation, migration and invasion. Next, online bioinformatics analysis and luciferase reporter were used to predict and validate the targeting relationship of miR-185-5p and RAB35. Finally, tumor cell-derived exosomes with genetic downregulation of RAB35 or overexpression of miR-185-5p were co cultured with their parental cells to verify the regulatory role of RAB35 on exosome secretion and function. Results: In NSCLC tissues and cell lines, miR-185-5p was downregulated, while RAB35 was significantly upregulated. Overexpression of miR-185-5p or knockdown of RAB35 expression inhibited cell proliferation, migration and invasion. Furthermore, we elucidated that RAB35 is a direct target of miR-185-5p. Additionally, exosomes derived from tumor cells restored cell proliferation, migration and invasion, whereas exosomes secreted by tumor cells with downregulation of RAB35 expression or overexpression of miR-185-5p lost their ability to restore cell proliferation, migration and invasion. Conclusions: Our results demonstrate that miR-185-5p inhibits tumor cell-derived exosomes-mediated proliferation, migration and invasion of NSCLC cells by downregulating RAB35 expression.

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“…Given the molecular and biological similarities between human and canine osteosarcomas 12,16 , a spontaneous canine model was used for our studies. Our immediate next experiments were thus devoted to characterizing canine osteosarcoma-derived exosomes and to confirm their conserved roles in the biology of the disease 6,7 . We first validated exosome production by canine osteosarcoma cell lines using immunofluorescence (IF).…”

Section: Exosome Production By Osteosarcoma Cells Is Positively Correlated With Tumormentioning

confidence: 99%

Development of an exosomal gene signature to detect residual disease in dogs with osteosarcoma using a novel xenograft platform and machine learning

Makielski

Donnelly

Khammanivong

et al. 2021

Preprint

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Osteosarcoma has a guarded prognosis. A major hurdle in developing more effective osteosarcoma therapies is the lack of disease specific biomarkers to predict risk, prognosis, or therapeutic response. Exosomes are secreted extracellular microvesicles emerging as powerful diagnostic tools. However, their clinical application is precluded by challenges in identifying disease associated cargo from the vastly larger background of normal exosome cargo. We developed a method using canine osteosarcoma in mouse xenografts to distinguish tumor derived from host response exosomal mRNAs. The model allows for the identification of canine osteosarcoma specific gene signatures by RNA sequencing and a species differentiating bioinformatics pipeline. An osteosarcoma-associated signature consisting of five gene transcripts (SKA2, NEU1, PAF1, PSMG2, and NOB1) was validated in dogs with spontaneous osteosarcoma by qRT PCR, while a machine learning model assigned dogs into healthy or disease groups. Serum/plasma exosomes were isolated from 53 dogs in distinct clinical groups (healthy, osteosarcoma, other bone tumor, or non neoplastic disease). Pre treatment samples from osteosarcoma cases were used as the training set and a validation set from post treatment samples was used for testing, classifying as osteosarcoma detected or osteosarcoma NOT detected. Dogs in a validation set whose post treatment samples were classified as osteosarcoma NOT detected had longer remissions, up to 15 months after treatment. In conclusion, we identified a gene signature predictive of molecular remissions with potential applications in the early detection and minimal residual disease settings. These results provide proof-of-concept for our discovery platform and its utilization in future studies to inform cancer risk, diagnosis, prognosis, and therapeutic response.

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Exosomes: Dynamic Mediators of Extracellular Communication in the Tumor Microenvironment

Cited by 16 publications

References 87 publications

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of non-small cell lung cancer cells

Development of an exosomal gene signature to detect residual disease in dogs with osteosarcoma using a novel xenograft platform and machine learning

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