Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo

Jorfi, Samireh; Ansa-Addo, Ephraim; Kholia, Sharad; Stratton, Dan; Valley, Shaunelle; Lange, Sigrun; Inal, Jameel M.

doi:10.1038/srep13006

Cited by 82 publications

(93 citation statements)

References 42 publications

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“…In agreement with current literature, our group recently reported prostate cancer cells, PC3, to competently efflux docetaxel (DTX) by unloading into MVs, and thus contributing to drug resistance . However, using a calpain inhibitor (calpeptin) or siRNA ( CAPNS1 ) microvesiculation pathways can be blocked.…”

Section: Use Of Exosomes and Microvesicles (Emvs) And Exosome‐mimeticsupporting

confidence: 85%

“…Extracellular Vesicles (EVs) is a term that encompasses EMVs and apoptotic bodies. They are produced as part of normal cell homeostasis and functions are heavily dependent on the parental cell lineage and state of the cell at the time of their release . EMVs’ functions range from waste removal, to autocrine, paracrine and long distance cell‐to‐cell signalling.…”

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confidence: 99%

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The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

et al. 2017

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There is an urgent need to develop new combination therapies beyond existing surgery, radio- and chemo-therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immunosuppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis. One promising cancer immunotherapy discussed uses cationic liposomes carrying tumour RNA (RNA-lipoplexes) to provoke a strong anti-viral-like (cytotoxic CD8 ) anti-tumour immune response. Mesenchymal stem cell-derived EMVs, with their capacity to migrate towards inflammatory areas including solid tumours, have also been used. As tumour EMVs clearly exacerbate the tumour microenvironment, another therapy option could involve EMV removal. Affinity-based methods to deplete EMVs, including an immunodepletion, antibody-based affinity substrate, are therefore considered. Finally EMV and exosome-mimetic nanovesicles (NVs) delivery of siRNA or chemotherapeutic drugs that target tumours using peptide ligands for cognate receptors on the tumour cells are discussed. We also touch upon the reversal of drug efflux in EMVs from cancer cells which can sensitize cells to chemotherapy. The use of immunotherapy in combination with the advent of EMVs provides potent therapies to various cancers.

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Section: Use Of Exosomes and Microvesicles (Emvs) And Exosome‐mimeticsupporting

confidence: 85%

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confidence: 99%

The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

et al. 2017

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“…Once thought to be cellular debris, these TEVs contain a variety of signaling molecules that prime the host microenvironment for tumor progression[27–30]. More specifically, TEVs not only facilitate the evasion of immune responses and drug therapy, but also support the establishment of pre-metastatic niches[31–33]. TEVs have also been shown to promote myofibroblastic differentiation of stromal progenitor cells[34,35].…”

Section: Introductionmentioning

confidence: 99%

Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells

et al. 2017

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Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting. TEVs collected from MDA MB-231 human metastatic breast cancer cells (MDAs) promoted ASC myofibroblast differentiation in both 2-D and 3-D culture as indicated by increased alpha smooth muscle actin (α-SMA) and fibronectin (Fn) levels. Correspondingly, TEV-treated ASCs were more contractile, secreted more vascular endothelial growth factor (VEGF), and promoted angiogenic sprouting of human umbilical vein endothelial cells. These changes were dependent on transforming growth factor beta (TGF-β)-related signaling and tumor cell glutaminase activity as their inhibition decreased TEV-related myofibroblastic differentiation of ASCs and related functional consequences. In summary, our data suggest that TEVs are important signaling factors that contribute to ASC desmoplastic reprogramming in the tumor microenvironment, and suggest that tumor cell glutamine metabolism may be used as a therapeutic target to interfere with this process.

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“…Inhibition of actin-related proteins suppressed the release of MVs from cells. One of the MV inhibitors with this mechanism of action is calpeptin (230, 231), an inhibitor of calpain. Calpain-mediated destabilization of the cortical actin cytoskeleton is essential for MV biogenesis.…”

Section: Translational Applications Of Evs In Cancermentioning

confidence: 99%

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

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et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Extracellular vesicles (EVs) have emerged as important players of cancer initiation and progression through cell-cell communication. They have been recognized as critical mediators of extracellular communications, which promote transformation, growth invasion, and drug-resistance of cancer cells. Interestingly, the secretion and uptake of EVs are regulated in a more controlled manner than previously anticipated. EVs are classified into three groups, (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on their sizes and origins, and novel technologies to isolate and distinguish these EVs are evolving. The biologically functional molecules harbored in these EVs, including nucleic acids, lipids, and proteins, have been shown to induce key signaling pathways in both tumor and tumor microenvironment (TME) cells for exacerbating tumor development. While tumor cell-derived EVs are capable of reprogramming stromal cells to generate a proper tumor cell niche, stromal-derived EVs profoundly affect the growth, resistance, and stem cell properties of tumor cells. This review summarizes and discusses these reciprocal communications through EVs in different types of cancers. Further understanding of the patcment of tumor specific therapeutics. This review will also discuss the translational aspects of EVs and therapeutic opportunities of utilizing EVs in different cancer types.

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Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo

Cited by 82 publications

References 42 publications

The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

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