Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

Li, Shenglong; Wang, Wei

doi:10.3389/fcell.2021.639514

Cited by 6 publications

(8 citation statements)

References 139 publications

(123 reference statements)

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“…Recent studies on breast cancer have revealed that several miRNAs contained in EVs contribute to osteoclast differentiation and osteolytic metastasis 26 . Wu et al 29 showed that bone‐tropic estrogen receptor–positive breast cancer cell–derived exosomal miR‐19a and integrin‐binding sialoprotein enhanced the differentiation of osteoclasts and bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies on breast cancer have revealed that several miRNAs contained in EVs contribute to osteoclast differentiation and osteolytic metastasis. 26 Wu et al 29 showed that bone-tropic is overexpressed in various human cancers and is upregulated in serum exosomes from patients with advanced breast cancer. 19,30 We found that miR-92a-3p was the most abundant miRNA in both cells and EVs of 4T1-EVs.…”

Section: Discussionmentioning

confidence: 99%

“… 24 The appearance of aberrantly activated osteoclasts induced via intercellular communication between metastasized tumor cells and bone microenvironments leads to osteolytic bone destruction. 5 Previous studies indicated that tumor cell–derived EVs are key mediators of intercellular communication between metastasized tumor cells and bone microenvironments 25 , 26 ; however, how they regulate osteoclast differentiation and function has not yet been fully elucidated. In this study, we demonstrated that 4T1‐EVs promote osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

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miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

et al. 2022

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Aberrant osteoclast formation and activation are the hallmarks of osteolytic metastasis. Extracellular vesicles (EVs), released from bone metastatic tumor cells, play a pivotal role in the progression of osteolytic lesions. However, the mechanisms through which tumor cell–derived EVs regulate osteoclast differentiation and function have not been fully elucidated. In this study, we found that 4T1 bone metastatic mouse mammary tumor cell–derived EVs (4T1‐EVs) are taken up by mouse bone marrow macrophages to facilitate osteoclastogenesis. Furthermore, treatment of mature osteoclasts with 4T1‐EVs promoted bone resorption, which was accompanied by enhanced survival of mature osteoclasts through the negative regulation of caspase‐3. By comparing the miRNA content in 4T1‐EVs with that in 67NR nonmetastatic mouse mammary tumor cell–derived EVs (67NR‐EVs), miR‐92a‐3p was identified as one of the most enriched miRNAs in 4T1‐EVs, and its transfer into mature osteoclasts significantly reduced apoptosis. Bioinformatic and Western blot analyses revealed that miR‐92a‐3p directly targeted phosphatase and tensin homolog (PTEN) in mature osteoclasts, resulting in increased levels of phospho‐Akt. Our findings provide novel insights into the EV‐mediated regulation of osteoclast survival through the transfer of miR‐92a‐3p, which enhances mature osteoclast survival via the Akt survival signaling pathway, thus promoting bone resorption.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

et al. 2022

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“…(3) randomized controlled trial (RCT). Exclusion criteria were (1) animal studies; (2) retrospective studies; (3) protocols; (4) studies without HuoxueHuayu therapy; (5) systematic reviews and meta-analyses; (6) abstract alone; (7) not cancer or irrelevant subject; (8) incomplete data; (9) duplicate articles.…”

Section: Eligibility Criteriamentioning

confidence: 99%

Effectiveness and Safety of the Traditional Chinese Medicine Treatment (HuoxueHuayu Therapy) for Malignant Tumors: A Systematic Review and Meta-Analysis

Chen

Wang

Yue

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. A malignant tumor is one of the refractory diseases that threaten human life and health. HuoxueHuayu therapy (one of the Traditional Chinese Medicine therapies to promote blood circulation and remove blood stasis) is widely used as an antitumor supplementary method. However, its efficacy and safety are still controversial. Therefore, the objective of this study was to provide evidence-based evidence for HuoxueHuayu therapy in the treatment of malignant tumors and confirm its safety and effectiveness. Methods. A systematic search in 8 electronic databases targeted randomized clinical studies evaluating HuoxueHuayu therapy for response evaluation, tumor progression rate, quality of life (QoL), peripheral hemogram, performance status, immunologic function, tumor marker, and blood coagulation function in cancer patients, published from the establishment of the database to December 31, 2020. Risk ratio (RR) was used for counting data, mean difference (MD) or standardized mean difference (SMD) was used for measurement data, and 95% confidence interval (CI) was used as efficacy analysis statistics. Results. Our search identified 69 studies, evaluating 4402 patients in total. Randomized controlled trials (RCTs) evaluated gastric (n = 14), lung (n = 18), pancreatic (n = 2), colorectal (n = 10), liver (n = 14), breast (n = 2), ovarian (n = 2), gallbladder (n = 1), esophagus (n = 1), and combined (n = 14) cancers and hematological malignancies (n = 2). The duration of HuoxueHuayu therapy ranged from 3 to 48 weeks. Methodological bias was low in 64 studies and high in 5 studies. HuoxueHuayu therapy was associated with significant improvement in response evaluation (Response Evaluation Criteria in Solid Tumor (RECIST): RR: 1.44, 95% CI: 1.27 to 1.63, I2 = 0%, n = 33 studies; World Health Organization Criteria in Solid Tumors (WHOCIST): RR: 1.40, 95% CI: 1.23 to 1.59, I2 = 0%, n = 26 studies), recurrence rate (RR: 0.85, 95% CI: 0.72 to 0.99, I2 = 0%, n = 2 studies), quality of life, performance status (MD: 5.60, 95% CI: 5.04 to 6.15, p < 0.001 ), immunologic function (CD3: SMD: 1.23, 95% CI: 0.79 to 1.66, p < 0.001 ; CD4: SMD: 1.25, 95% CI: 0.77 to 1.74, p < 0.001 ; CD4/CD8: SMD: 1.05, 95% CI: 0.69 to 1.42, p < 0.001 ; natural killer cell (NK): SMD: 0.74, 95% CI: 0.32 to 1.15, p < 0.001 ), tumor marker, and blood coagulation function (D-dimer (D-D); fibrinogen (FIB)). In addition, HuoxueHuayu therapy could reduce toxicity caused by chemotherapy and radiotherapy without risks of liver and kidney injury or bleeding, although the effect on tumor metastasis was uncertain. Conclusions. The present update of our systematic review and meta-analyses provided essential evidence for the beneficial effect of HuoxueHuayu therapy to show promise in cancer treatment, improving quality of life, addressing cancer-related symptoms, and reducing toxicity in a secure way.

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“…They can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed metastasis [17]. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area [18]. The emerging evidence on EV functions in bone metastasis will facilitate the discovery of novel treatments [19].…”

Section: Introductionmentioning

confidence: 99%

The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

2021

J Nanobiotechnol

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Bone sarcomas are rare cancers accompanied by metastatic disease, mainly including osteosarcoma, Ewing sarcoma and chondrosarcoma. Extracellular vesicles (EVs) are membrane vesicles released by cells in the extracellular matrix, which carry important signal molecules, can stably and widely present in various body fluids, such as plasma, saliva and scalp fluid, spinal cord, breast milk, and urine liquid. EVs can transport almost all types of biologically active molecules (DNA, mRNA, microRNA (miRNA), proteins, metabolites, and even pharmacological compounds). In this review, we summarized the basic biological characteristics of EVs and focused on their application in bone sarcomas. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. The role of EVs in bone sarcoma has been analyzed point-by-point. In the microenvironment of bone sarcoma, bone sarcoma cells, mesenchymal stem cells, immune cells, fibroblasts, osteoclasts, osteoblasts, and endothelial cells coexist and interact with each other. EVs play an important role in the communication between cells. Based on multiple functions in bone sarcoma, this review provides new ideas for the discovery of new therapeutic targets and new diagnostic analysis.

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Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

Cited by 6 publications

References 139 publications

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

Effectiveness and Safety of the Traditional Chinese Medicine Treatment (HuoxueHuayu Therapy) for Malignant Tumors: A Systematic Review and Meta-Analysis

The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

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