Exosomal particles secreted by prostate cancer cells are potent mRNA and protein vehicles for the interference of tumor and tumor environment

Rauschenberger, Lisa; Staar, Doreen; Thom, Kathleen; Scheffold, Christian; Venz, Simone; Homuth, Georg; Schlüter, Rabea; Brandenburg, Lars‐Ove; Ziegler, Patrick; Zimmermann, Uwe; Weitschies, Werner; Völker, Uwe; Lendeckel, Uwe; Walther, Reinhard; Burchardt, Martin; Stope, Matthias B.

doi:10.1002/pros.23132

Cited by 20 publications

(13 citation statements)

References 51 publications

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“…In prostate cancer cells, HSP27 protein is unspecifically incorporated into exosomes [22], and in OC cells, Dolo et al identified a protein release by cellular vesicle shedding [42]. The data presented here explicitly demonstrated the incorporation of HSP27 into exosomes, thereby liberating the protein from OC cells by bypassing the classical endoplasmic reticulum secretory pathway.…”

Section: Discussionmentioning

confidence: 67%

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Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

et al. 2017

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The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker.

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Section: Discussionmentioning

confidence: 67%

“…Preparation of exosomes was followed as previously described [22]. Briefly, cells were incubated in T75 cell culture flasks with 20 ml cell culture medium and exposed to the heat shock cycle.…”

Section: Methodsmentioning

confidence: 99%

Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

et al. 2017

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“…Regarding genetic biomolecules, RNAs including messenger RNAs (mRNAs) and microRNAs (miRNAs) have also been found in EVs which have been increasingly found to elicit various functions in recipient cells [11,82,83,84,85,86,87,88,89,90]. In particular, large amounts of mRNAs and miRNAs were found in all three EV types released from both cell cultures and body fluids [14,82,83,84,87,88,89,90].…”

Section: Functional Components Of Evsmentioning

confidence: 99%

Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing

Than

Guanzon

Leavesley

et al. 2017

IJMS

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Extracellular vesicles (EVs) are membrane-enclosed vesicles that are released into the extracellular environment by various cell types, which can be classified as apoptotic bodies, microvesicles and exosomes. EVs have been shown to carry DNA, small RNAs, proteins and membrane lipids which are derived from the parental cells. Recently, several studies have demonstrated that EVs can regulate many biological processes, such as cancer progression, the immune response, cell proliferation, cell migration and blood vessel tube formation. This regulation is achieved through the release and transport of EVs and the transfer of their parental cell-derived molecular cargo to recipient cells. This thereby influences various physiological and sometimes pathological functions within the target cells. While intensive investigation of EVs has focused on pathological processes, the involvement of EVs in normal wound healing is less clear; however, recent preliminarily investigations have produced some initial insights. This review will provide an overview of EVs and discuss the current literature regarding the role of EVs in wound healing, especially, their influence on coagulation, cell proliferation, migration, angiogenesis, collagen production and extracellular matrix remodelling.

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“…Late endosomes/MVBs can be triggered to fuse with the cell surface and release their intraluminal vesicles. Along with several other proteins such as Flotillin2 and HSP70, the tetraspanins CD63 and CD9 are commonly used markers for exosomes [47]. However, the mechanism of exosome formation, secretion and uptake, as well as the physiological significance of exosomal content remain to be understood.…”

Section: Hypoxia-mediated Release Of Exosomes In the Ovarian Tumor Enmentioning

confidence: 99%

The biological significance and clinical applications of exosomes in ovarian cancer

Dorayappan¹,

Wallbillich²,

Cohn

et al. 2016

Gynecologic Oncology

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Exosomes are nano-sized (20–100 nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer.

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Exosomal particles secreted by prostate cancer cells are potent mRNA and protein vehicles for the interference of tumor and tumor environment

Abstract: The results reveal a distinct exosomal functionality in the modulation of the prostatic tumor adjacent environment. The multitude of translocated factors implies the induction of numerous effects in tumor-associated target cells, including impact on cellular growth.

Cited by 20 publications

References 51 publications

Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27’s Phosphorylation Status, and Is Mediated by Exosome Liberation

Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing

The biological significance and clinical applications of exosomes in ovarian cancer

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