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Exosomes: Novel Players of Therapy Resistance in Neuroblastoma

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1277))

Abstract

Neuroblastoma is a solid tumor (a lump or mass), often found in the small glands on top of the kidneys, and most commonly affects infants and young children. Among neuroblastomas, high-risk neuroblastomas are very aggressive and resistant to most kinds of intensive treatment. Immunotherapy, which uses the immune system to fight against cancer, has shown great promise in treating many types of cancer. However, high-risk neuroblastoma is often resistant to this approach as well. Recent studies revealed that small vesicles known as exosomes, which are envelopes, could deliver a cargo of small RNA molecules and provide communication between neuroblastoma cells and the surrounding cells and trigger metastasis and resistance to immunotherapy. In this chapter, we describe the role of exosomes and small RNA molecules in the metastasis and regression of neuroblastoma and the potential therapeutic approaches to combat this menace.

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Abbreviations

3′-UTR :

Three prime untranslated region

ADCC :

Antibody-dependent cell cytotoxicity

AURKA:

Aurora kinase A

EFS:

Event-free survival

ESCRT:

Endosomal-sorting complex required for transport

GD2:

Disialoganglioside

IL-15:

Interleukin-15

IL-2:

Interleukin-2

ILV:

Intraluminal vesicle

MAb :

Monoclonal antibody

miRNA:

MicroRNA

mRNA:

Messenger RNA

MSCs:

Mesenchymal stem/stromal cells

MVBs :

Multivesicular bodies

MYCN :

v-myc myelocytomatosis viral-related oncogene, neuroblastoma-derived

NEDD4:

Neuronal precursor cell-expressed developmentally downregulated 4

NF-κB:

Nuclear factor-kappa B

NK :

Natural killer

PCR:

Polymerase chain reaction

PNTs :

Peripheral neuroblastic tumors

RNA :

Ribonucleic acid

TERF1:

Telomeric repeat-binding factor 1

TGFβ 1:

Transforming growth factor beta 1

TGFβR1:

Transforming growth factor beta receptor 1

TGFβR2:

Transforming growth factor beta receptor 2

TLR8 :

Toll-like receptor 8

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Acknowledgments

Dr. Challagundla’s laboratory is supported in whole or part from the NIH/NCI grant (K22CA197074-01); Leukemia Research Foundation (LRF) grant, the Nebraska State DHHS (LB506); UNMC Pediatric Cancer Research Center; Fred and Pamela Buffett Cancer Center’s pilot grant (P30 CA036727) in conjunction with the UNMC Pediatric Cancer Research Center; and the Department of Biochemistry and Molecular Biology start-up. Heather Richard and Arya Pokhrel are thankful to Terri L. Gulick, Jaynie E. Bird, Michele Merrill, and Heidi N. Kaschke and acknowledge the support of the UNMC High School Alliance Health Sciences Enrichment Program.

Conflict of Interest

The authors declare no conflict of interest.

Author information

Author notes

  1. Heather Richard and Arya Pokhrel contributed equally.

Authors and Affiliations

  1. High School Alliance Health Sciences Enrichment Program, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Heather Richard & Arya Pokhrel

  2. Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Srinivas Chava, Anup Pathania & Kishore B. Challagundla

  3. REVA University, Rukmini Knowledge Park Kattigenahalli, Yelahanka, Bangalore, Karnataka, India

    Santharam S. Katta

  4. The Children’s Health Research Institute, University of Nebraska Medical Center, Omaha, NE, USA

    Kishore B. Challagundla

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Correspondence to Kishore B. Challagundla .

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Editors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Richard, H., Pokhrel, A., Chava, S., Pathania, A., Katta, S.S., Challagundla, K.B. (2020). Exosomes: Novel Players of Therapy Resistance in Neuroblastoma. In: Birbrair, A. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1277. Springer, Cham. https://doi.org/10.1007/978-3-030-50224-9_5

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