PGRN−/− TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration

Yue, Shujun; Ye, Xiangsen; Zhou, Ting; Gan, Delu; Qian, Husun; Fang, Wenli; Yao, Mengli; Zhang, Dian; Shi, He; Chen, Tingmei

doi:10.1016/j.lfs.2020.118687

Cited by 39 publications

(23 citation statements)

References 45 publications

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“…Exosomes derived from breast cancer cells have upregulated levels of miR-130 and miR-33, which can alter the polarization of macrophages from M2 to M1 phenotype and inhibit tumor progression (100). The exosomes derived from TAMs of progranulin (PGRN)-negative tumor tissues have upregulated expression of miR-5100, which inhibits the invasion, migration and EMT of breast cancer cells by targeting the CXCL12/CXCR4 axis (101). Although a similar study in ovarian cancer has not been performed, studies have shown that expression of PGRN protein relates to poor ovarian cancer prognosis (102,103).…”

Section: Immune Cellsmentioning

confidence: 99%

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

et al. 2021

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Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.

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Section: Immune Cellsmentioning

confidence: 99%

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

et al. 2021

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“…In recent years, the importance of gene therapy has been widely recognized in PC research due to it highly targeted effects and fewer side effects. Gene therapy can inhibit the growth of PC cells by regulating the protein expression of targeted genes, and PC therapy based on miRNAs is a research hotspot in this field ( Li N. et al, 2020 ; Yue et al, 2020 ; An et al, 2021 ). MiRNAs can bind to the 3′ untranslated region of the targeted gene mRNA and can regulate the expression of downstream target genes.…”

Section: Discussionmentioning

confidence: 99%

MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV

Zhu

et al. 2021

Front. Cell Dev. Biol.

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Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 μg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.

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“…Other exosomal miRNAs that inhibit cancer cell proliferation, migration and invasion are miR-140-3p which targets BCL9 and BCL2; and miR-5100, which regulates the expression of CXCL12, thus inhibiting the CXCL12/CXCR4 axis, which is used by some cancer cells to spread to regional nodes of the primary tumor [257,258].…”

Section: Potential Role Of Exosomes In Cancer Treatmentmentioning

confidence: 99%

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

et al. 2021

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Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

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PGRN−/− TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration

Cited by 39 publications

References 45 publications

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

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