scholarly journals Current Strategies for Cancer Cell-Derived Extracellular Vesicles for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Weijian Lin ◽  
Xing-Dong Cai
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Genetically Engineered ◽  
Bioactive Molecules ◽  
Advanced Materials ◽  
Direct Extraction ◽  
Innovative Strategies ◽  
Tumor Drugs ◽  
Tumor Area

Cancer cell-derived extracellular vesicles (CEVs), a novel type of therapeutic agent in cancer treatment, can be prepared from the autocrine secretion of various cancer cells, the direct extraction of cancer cells and the combination of cancer cell-derived membranes with advanced materials. With various bioactive molecules, exosomes are produced by cells for intercellular communication. Although cancer cell-derived exosomes are known to inhibit tumor apoptosis and promote the progression of cancer, researchers have developed various innovative strategies to prepare anti-tumor vesicles from cancer cells. With current strategies for anti-tumor vesicles, four different kinds of CEVs are classified including irradiated CEVs, advanced materials combined CEVs, chemotherapeutic drugs loaded CEVs and genetically engineered CEVs. In this way, CEVs can not only be the carriers for anti-tumor drugs to the target tumor area but also act as immune-active agents. Problems raised in the strategies mainly concerned with the preparation, efficacy and application. In this review, we classified and summarized the current strategies for utilizing the anti-tumor potential of CEVs. Additionally, the challenges and the prospects of this novel agent have been discussed.

scholarly journals Gestational Tissue-Derived Human Mesenchymal Stem Cells Use Distinct Combinations of Bioactive Molecules to Suppress the Proliferation of Human Hepatoblastoma and Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Nitchapon Paiboon ◽  
Witchayaporn Kamprom ◽  
Sirikul Manochantr ◽  
Chairat Tantrawatpan ◽  
Duangrat Tantikanlayaporn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Mesenchymal Stem Cells ◽  
Bioactive Molecules ◽  
Mass Spectrometry Analysis ◽  
Cancer Cell Proliferation ◽  
Protein Fractionation ◽  
Spectrometry Analysis ◽  
Colorectal Cancer Cells

Background. Cancer has been considered a serious global health problem and a leading cause of morbidity and mortality worldwide. Despite recent advances in cancer therapy, treatments of advance stage cancers are mostly ineffective resulting in poor survival of patients. Recent evidences suggest that multipotent human mesenchymal stem cells (hMSCs) play important roles in growth and metastasis of several cancers by enhancing their engraftment and inducing tumor neovascularization. However, the effect of hMSCs on cancer cells is still controversial because there are also evidences demonstrating that hMSCs inhibited growth and metastasis of some cancers. Methods. In this study, we investigated the effects of bioactive molecules released from bone marrow and gestational tissue-derived hMSCs on the proliferation of various human cancer cells, including C3A, HT29, A549, Saos-2, and U251. We also characterized the hMSC-derived factors that inhibit cancer cell proliferation by protein fractionation and mass spectrometry analysis. Results. We herein make a direct comparison and show that the effects of hMSCs on cancer cell proliferation and migration depend on both hMSC sources and cancer cell types and cancer-derived bioactive molecules did not affect the cancer suppressive capacity of hMSCs. Moreover, hMSCs use distinct combination of bioactive molecules to suppress the proliferation of human hepatoblastoma and colorectal cancer cells. Using protein fractionation and mass spectrometry analysis, we have identified several novel hMSC-derived factors that might be able to suppress cancer cell proliferation. Conclusion. We believe that the procedure developed in this study could be used to discover other therapeutically useful molecules released by various hMSC sources for a future in vivo study.

scholarly journals Mesenchymal stem cell-derived extracellular vesicles may promote breast cancer cell dormancy

2018 ◽  
Vol 9 ◽  
pp. 204173141881009 ◽  
Author(s):  
Jake Casson ◽  
Owen G Davies ◽  
Carol-Anne Smith ◽  
Matthew J Dalby ◽  
Catherine C Berry
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Cell Dormancy

Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, while upregulating cell adhesion, thus retaining the cancer cells within the bone marrow microenvironment. Here, MCF7 breast cancer cells were treated with mesenchymal stem cell–derived extracellular vesicles, resulting in reduced migration in two-dimensional and three-dimensional culture, with reduced cell proliferation and enhanced adhesion, collectively supporting cancer cell dormancy.

scholarly journals Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Qian Zhang ◽  
Xiangling Yang ◽  
Huanliang Liu
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Bioactive Molecules ◽  
Diagnosis And Treatment ◽  
Existing Problems ◽  
Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

scholarly journals Proteomic profiling of extracellular vesicles and particles reveals the cellular response to cisplatin in NSCLC

2021 ◽  
Author(s):  
Jiaqi Xu ◽  
Lujuan Wang ◽  
Na Yin ◽  
Anqi Chen ◽  
Junqi Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Building Blocks ◽  
Proteomic Profiling ◽  
Transcriptional Profiles ◽  
Dormant State ◽  
Activated State

Abstract Background Cisplatin-based chemotherapy is a first-line therapeutic strategy against Non Small Cell Lung Cancer. However, cancers relapse months or years after chemotherapy due to a dormant state of residual cancer cells. Great efforts have been made to identify biomarkers that can be used to predict the relapse after a peroid of dormancy. Extracellular vesicles and extracellular particles (EVPs) have been considered to be active carriers of proteins and nucleic acid. Methods The proteome of lung cancer cells in dormant and reactivated states after treatement of cisplatin was analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS).Then we compared the EVPs from cisplatin-responsive cancer cells and their gene transcriptional profiles. Results We found that apolipoproteins such as APOA1, APOE were significantly increased in dormant cancer cell-derived EVPs.Integration of EVP proteomes with transcriptional profiles of cancer cells revealed that the proteomic profiling of EVP derived from cancer cells can reflect the cellular status of cancer cells, which showed an activated lipid metabolism in dormant state. The activated lipid metabolism may provide the building blocks necessary for the following cancer cell proliferation in activated state. Conclusions Taken together,our study found that lipoproteins enriched in EVPs reflect the activated lipid metabolism in dormant cancer cells. It will provide predictive biomarkers or therapeutic targets for cisplatin-induced dormant cancer cells.

scholarly journals Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Chong Lu ◽  
Yu Zhao ◽  
Jing Wang ◽  
Wei Shi ◽  
Fang Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Cancer Tissues

Abstract Background Extracellular vesicles (EVs) derived from tumor cells are implicated in the progression of malignancies through the transfer of molecular cargo microRNAs (miRNAs or miRs). We aimed to explore the role of EVs derived from breast cancer cells carrying miR-182-5p in the occurrence and development of breast cancer. Methods Differentially expressed miRNAs and their downstream target genes related to breast cancer were screened through GEO and TCGA databases. miR-182-5p expression was examined in cancer tissues and adjacent normal tissues from patients with breast cancer. EVs were isolated from breast cancer cell line MDA-MB-231 cells and identified. The gain- and loss-of function approaches of miR-182-5p and CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) were performed in MDA-MB-231 cells and the isolated EVs. Human umbilical vein endothelial cells (HUVECs) were subjected to co-culture with MDA-MB-231 cell-derived EVs and biological behaviors were detected by CCK-8 assay, flow cytometry, immunohistochemical staining, Transwell assay and vessel-like tube formation in vitro. A xenograft mouse model in nude mice was established to observe the tumorigenesis and metastasis of breast cancer cells in vivo. Results miR-182-5p was highly expressed in breast cancer tissues and cells, and this high expression was associated with poor prognosis of breast cancer patients. miR-182-5p overexpression was shown to promote tumor angiogenesis in breast cancer. Moreover, our data indicated that miR-182-5p was highly enriched in EVs from MDA-MD-231 cells and then ultimately enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro and in vivo. Moreover, we found that CMTM7 is a target of miR-182-5p. EVs-miR-182-5p promotes tumorigenesis and metastasis of breast cancer cells by regulating the CMTM7/EGFR/AKT signaling axis. Conclusions Taken altogether, our findings demonstrates that EVs secreted by breast cancer cells could carry miR-182-5p to aggravate breast cancer through downregulating CMTM7 expression and activating the EGFR/AKT signaling pathway.

scholarly journals Extracellular vesicles induce aggressive phenotype of luminal breast cancer cells by PKM2 phosphorylation

2021 ◽  
Author(s):  
Seo Young Kang ◽  
Eun Ji Lee ◽  
Jung Woo Byun ◽  
Dohyun Han ◽  
Yoori Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Extracellular Vesicles ◽  
Aerobic Glycolysis ◽  
Serine Phosphorylation ◽  
Mcf7 Cells ◽  
Glycolytic Activity

AbstractThe aerobic glycolysis is a hallmark of cancer glucose metabolism. Several studies have suggested that cancer-derived extracellular vesicles (EVs) can modulate glucose metabolism in adjacent cells and promote disease progression. Here we suggest that EVs originated from cancer cell with highly glycolytic activity can modulate glucose metabolism in the recipient cancer cells with relative low glycolytic activity, and further induce cell proliferation. Two types of breast cancer cell lines with different levels of glycolytic activity, MDA-MB-231 of a claudin low-type breast cancer cell and MCF7 of luminal type breast cancer cell, were selected and co-cultured using indirect co-culture system such as transwell system or microfluidic system. Glucose uptake of the recipient MCF7 cells was markedly increased after co-culture with MDA-MB-231 cells. MCF7 cells after co-culture with MDA-MB-231-tdTomato cells represented multiple tdTomato signal inside the cell, which proved that EVs originated from MDA-MB-231-tdTomato were transferred to MCF7 cell. In addition, serine phosphorylation of PKM2 necessary for tumorigenesis was highly activated, and tyrosine phosphorylation of PKM2 suggesting activated aerobic glycolysis was also increased in the co-cultured MCF7 cells. Proteomic profiling of the co-cultured MCF7 cells revealed the proliferation and dedifferentiation of MCF7 cells, and further confirmed epithelial-mesenchymal transition (EMT), which is a key phenomenon for cancer metastasis. In the transcriptomic analysis, glycolysis increased in co-cultured MCF7 cells, and the component analysis of genes associated with glycolysis revealed that the next major component after cytoplasm was extracellular exosome. Proteomic analysis of EVs revealed that there were important proteins in the EV such as EGFR, ERBB2 and MAPK for phosphorylating PKM2. This phenomenon suggests the potential for aggressive cancer cells to affect other cancer cells through EV mediators.

Experimental Evidence in Support of the Dormant Cancer Cell

1967 ◽  
Vol 53 (4) ◽  
pp. 373-378 ◽  
Author(s):  
Domenico Agostino
Keyword(s):  
Experimental Evidence ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Vena Cava ◽  
Dormant Cell ◽  
Aortic Blood ◽  
Tumor Area

Cancer cells were identified circulating in the vena cava and aortic blood of animals bearing a cecal tumor. Tumor takes were obtained in only 2% of the animals inoculated subcutaneously with 2000 cancer cells. If however they were subjected to repeated laparotomies and massage of the tumor area the takes were increased to 48% of the animals. These studies demonstrate that stress applied by many means can reduce the host resistence to an extent that the dormant cell could riactivate and reproduce the tumor.

scholarly journals AMIGO2 Contained in Cancer Cell-derived Small Extracellular Vesicles Enhances the Adhesion of Liver Endothelial Cells to Cancer Cells

2021 ◽  
Author(s):  
Runa Izutsu ◽  
Mitsuhiko Osaki ◽  
Hideyuki Nemoto ◽  
Maho Jingu ◽  
Ryo Sasaki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Liver Metastasis ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Cancer Metastasis ◽  
Vascular Endothelial Cells ◽  
Gastric Cancer Cells ◽  
Liver Endothelial Cells

Abstract Adhesion of cancer cells to vascular endothelial cells in target organs is an initial step in cancer metastasis. Our previous studies revealed that amphoterin-induced gene and open reading frame 2 (AMIGO2) promotes the adhesion of tumor cells to liver endothelial cells, followed by the formation of liver metastasis in a mouse model. However, the precise mechanism underlying AMIGO2-promoted the adhesion of tumor cells and liver endothelial cells remains unknown. This study was conducted to explore the role of cancer cell-derived AMIGO2-containing small extracellular vesicles (sEVs) in the adhesion of cancer cells to human hepatic sinusoidal endothelial cells (HHSECs). Western blotting indicated that AMIGO2 was present in sEVs from AMIGO2-overexpressing MKN-28 gastric cancer cells. The efficiency of sEV incorporation into HHSECs was independent of the AMIGO2 content in sEVs. When sEV-derived AMIGO2 was internalized in HHSECs, it significantly enhanced the adhesion of HHSECs to gastric (MKN-28 and MKN-74) and colorectal cancer cells (SW480), all of which lacked AMIGO2 expression. Thus, we identified a novel mechanism by which sEV-derived AMIGO2 released from AMIGO2-expressing cancer cells stimulates endothelial cell adhesion to different cancer cells for the initiate step of liver metastasis.

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