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A special issue of Journal of Cancer Metastasis and Treatment

ISSN 2454-2857 (Online), ISSN 2394-4722 (Print)

Submission deadline: 31 May 2020

Guest Editor(s)

Submission Deadline

31 May 2020

Planned Papers

Type: Review

Title: The good and bad sides of exosomes: from pro-metastatic to cancer biomarkers and therapy carriers

Authors: Isabella Panfoli and Maurizio Bruschi

Affiliations: 1Dipartimento di Farmacia-DIFAR, Università di Genova, Genoa, Italy;
2Laboratory of Molecular Nephrology, Istituto Giannina Gaslini, Genoa, Italy.

Abstract: Exosomes, nanovesicles of endocytic origin, are secreted by most cell types; cancer cells represent no exception. Exosomes facilitate intercellular communication as they deliver diverse proteins, mRNA, miRNA and lipids. In this review, we discuss how exosomes represent one of the main risks associated with cancer but also one of the most promising new tools to fight it. Exosomes function as signalling molecules between the tumor microenvironment, i.e. the complex of both tumor and stromal cells, and the rest of the body. Tumor-derived exosomes are shown to drive the initiation and progression of metastasis, by directing their cargoes towards target tissues. In this respect, exosomes are implicated in cancer progression, dissemination and therapy resistance. However, exosomes are also emerging as a key tool in precision medicine, pivotal for cancer liquid biopsy in the early diagnostic and recurrence assessment applications. Profiling exosomal cancer-derived nucleic acids by ultrasensitive next generation sequencing is going to allow early cancer detection, therapeutic stratification and monitoring of response to therapy. Exosomes are also a promising new tool of cancer immunotherapy with its promising applications. The next years will witness the challenging clinical applications of exosomes in cancer diagnosis and therapeutics.

Type: Review

Title: Decoding the Role of Exosomes in Cancer Diseases

Authors: Fengyan Deng

Affiliations: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA

Abstract: Exosomes are nanovesicles (ranging from 30 nm to 150 nm), which are secreted by a variety of cell types under different normal and pathological conditions. As exosomes carry bioactive molecules from the originate cells and can traffic its cargos from the donor cells to receipt cells, it plays crucial roles in cell-to-cell communication. Emerging evidence has indicated that exosomes mediate the interaction between cancer cells and their microenvironment and play important roles in facilitating tumorigenesis of various cancer diseases by regulating angiogenesis, immunity, and metastasis. Furthermore, cancer cell derived exosomes have been identified in body fluids such as blood, urine, breast milk, bile, pancreatic juice, cerebrospinal, peritoneal fluids and saliva from patients with cancer, which highlights exosomes as potential diagnostic biomarkers. In addition, more and more scientists have been attracted by the therapeutic potential of exosomes: by delivering some special drugs to some specific tissues or cells, exosomes can serve as efficient drug carriers. In this review, we summarize the recent studies on the roles of tumor-derived exosomes in tumorigenesis, exosomal cancer biomarkers as well as the therapeutic methods.

Type: Review

Title: The effect of cell type and environment on exosome composition and cell-cell crosstalk

Authors: Rabab N. Hamzah1, 2, Alexandru S. Biris2, Robert J. Griffin1

Affiliations: 1Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205.
2Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, 72204.

Abstract: exosomes are extremely small vesicles averaging around 100 nm in diameter; secreted by different cell types; and contain proteins, lipids, and RNA packaged while in their donor cells. Reports in the literature suggest that exosomes may simply have the same functions as their donor cells. In addition, important new understanding on how exosomes communicate with other cells without any direct cell-cell interactions is rapidly accumulating. Recent data suggests that this communication depends on the exosome source. For example, are tumor cell exosomes taken up by all normal cells and cancer cells? Or are exosomes secreted by normal cells not taken up by normal cells or tumor cells? What is the possible reason for selectivity in exosome uptake? In this review, we will discuss the effect of exosome source and cellular environment on tumor and normal cell interaction and communication.

Type: Research Article

Title: Exosome-Stem cell co-cultures to guide stem cell differentiation

Authors: Rabab N. Hamzah1, 2, Alexandru S. Biris2, Robert J. Griffin1

Affiliations: 1Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205.
2Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, 72204.

Abstract: Exosomes are secreted by many, if not all, cell types, including normal, tumor, and stem cells. Each cell line secretes exosomes in different quantities, sizes, and cargo. In addition, the intended function of exosomes varies according to the donor cell properties. Several studies have analyzed the effect of exosome source on cell-cell interaction and cell communications, such as the effect of macrophage exosomes on communication with cancer cells. Many studies proved that cancer cells secrete exosomes into the tumor microenvironment and that breast tumor exosomes can stimulate metastasis and promote tumor growth. Despite a large increase in reports on the biological function of exosomes in different scenarios, the field still lacks clear understanding of the effect of exosomes on stem cell differentiation and how these cells interact with exosomes obtained from different cell types and conditions. Therefore, our work focuses on the interaction between human mesenchymal stem cells (hMSCs), rat neural stem cells (RNSCs), and neuronal cells with exosomes from human brain tumor cells (glioblastoma U87 cells) or from astrocytes to understand how vesicles from different cell types guide the differentiation pathway for stem cells. These studies offer significant insight into the effect of tumor growth and treatment response on normal brain function and recovery, increasing our knowledge of how to optimally use stem cells for transplant conditions.

Type: Review

Title: Exosomes in immune regulation

Authors: Heidi Schwarzenbach1, Peter B. Gahan2

Affiliations: 1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany 2Fondazione “Enrico Puccinelli” Onlus, Perugia 06123, Italy

Abstract: Exosomes, small extracellular vesicles, mediate intercellular communication by transferring their cargo including DNA, RNA, proteins and lipids from cell to cell. Notably, in the immune system, they have protective functions. However in cancer, exosomes acquire new, immunosuppressive properties causing the dysregulation of immune cells and immune escape of tumor cells supporting cancer progression and metastasis. Therefore, current investigations focus on the regulation of exosome levels for immunotherapeutic interventions. In this review, the role of exosomes in immunomodulation of lymphoid and myeloid cells and their use as immune stimulatory agents to elicit specific cytotoxic responses against the tumor are considered.

Type: Review

Title: Exosomes as a promising diagnostic tool in HNSCC?

Authors: K. Pastor, L. Muller

Affiliations: Department of Otolaryngology and Head&Neck Surgery and Department of Biomedicine, University Hospital Basel, Switzerland

Abstract: Head and Neck Squamous Cell Carcinoma (HNSCC) is the 6th most frequently diagnosed malignancy and is the reason for about 5% of all malignancies worldwide. There is a lack of biomarkers to monitor the status and progress of the disease. Therefore it is of high importance to develop non-invasive diagnostic tools such as exosomes which monitor the tumour change and provides with molecular information of the malignancy in order to identify the metastatic disease earlier for therapeutic management. Thus, we aim to review whether tumour derived exosomes (TEX) can prognosticate disease progression in HNSCC and to scrutinize if and especially how to use them as a diagnostic tool in the future.

Type: Review

Title: The two sides of the coin: the role of glioblastoma-derived exosomes inside and outside the CNS

Authors: Elisa Helena Farias Jandrey1, Marcelle Bezerra Silva Oliveira1, Frank Furnari2, Anamaria Aranha Camargo1, Érico Tosoni Costa1

Affiliations: 1Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo – SP, Brazil. 
2Ludwig Institute for Cancer Research (LICR), University of California, San Diego

Abstract: Glioblastoma (GBM) is the most common and lethal type of primary brain cancer in adults. Due to the selective protection provided by the blood-brain barrier (BBB) and the infiltrative nature of GBM cells in the brain parenchyma, therapeutic options are largely limited and no clinically validated circulating biomarkers for monitoring responsiveness exists. As a result, GBM remains incurable and most patients will succumb to the disease within 12-15 months of diagnosis. GBM-derived extracellular vesicles (EV), especially exosomes, play a critical role in GBM progression by mediating local immunosuppression and activating persistent invasive programs. Intriguingly, despite the unparalleled invasive potential of GBM cells through the brain, GBM rarely metastasizes to other tissues outside of the CNS. Despite this, GBM-derived EVs easily cross the intact BBB and are increased in the peripheral blood of patients in comparison with healthy controls. This raises the possibility that these EVs could also exhibit pleiotropic biological functions outside the CNS and may be used as a potential biomarker for diagnosis/prognosis for GBM patients. It is well know the role of exosomes in forming the pre-metastatic niches in secondary organs, like lungs and brain, in this review we explore the biological role of GBM-derived EVs inside and outside of CNS and discuss the current status of liquid biopsy and its advantages to manage the treatment of patients with GBM.

Type: Article

Title: Tumor cell-derived exosomes have a some roles in the occurrence and progression of cancer

Authors: Jin-Sook Seo, Eun-Kyeong Jang, Ju-Seop Kang

Affiliations: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul 04763, South Korea

Abstract: The present study attempted to explore the possibility that tumor cell-derived exosomes could initiate DNA damage through communication with normal cells or be involved in the metastasis cascade of cancer cells. Tumor cell-derived exosomes (exosome-mimics) were artificially produced as follows; cultured hepatoma cell line hep3B and sequentially passed through a 10, 5 and 1.0 μm filter using a mini extruder to experimentally produce exosome-mimics of 30-200μm size and confirmed the size and image. The experimental group was injected exosome-mimics into the peritoneum for 4 weeks in the normal BALB/c nude mice once (0.1mL, 1.0 × 105 cells)/day. The control group is administered intraperitoneally with culture medium. The other experimental group was administered subcutaneously with tumor cells. It was found to be involved in the development and metastasis of cancer. The serum alpha fetoprotein (AFP) was significantly increased in exosome-mimics and tumor cell-treated groups compared to control group. In addition, the expression of cancer-related genes (p53, p21, bcl-2 and ki-67) in the exosome-mimetic-treated group was observed in the same pattern as the tumor cell-treated group. In conclusion, tumor cell-derived exosomes were thought to be involved in cancer development and metastasis.

Published Articles

This special issue is now open for submission.
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